Glucuronidation: driving factors and their impact on glucuronide disposition

References

• Adlercreutz H, Markkanen H, Watanabe S. (1993). Plasma concentrations of phyto-oestrogens in Japanese men. Lancet 342:1209–1210.
   PubMed Web of Science ®Google Scholar
• Alfaras I, Perez M, Juan ME, et al. (2010). Involvement of breast cancer resistance protein (BCRP1/ABCG2) in the bioavailability and tissue distribution of trans-resveratrol in knockout mice. J Agric Food Chem 58:4523–4528.
   PubMed Web of Science ®Google Scholar
• Alvarez AI, Vallejo F, Barrera B, et al. (2011). Bioavailability of the glucuronide and sulfate conjugates of genistein and daidzein in breast cancer resistance protein 1 knockout mice. Drug Metab Dispos 39:2008–2012.
   PubMed Web of Science ®Google Scholar
• An G, Morris ME. (2011). The sulfated conjugate of biochanin A is a substrate of breast cancer resistant protein (ABCG2). Biopharm Drug Dispos 32:446–457.
   PubMed Web of Science ®Google Scholar
• Andersen G, Christrup L, Sjogren P. (2003). Relationships among morphine metabolism, pain and side effects during long-term treatment: an update. J Pain Symptom Manage 25:74–91.
   PubMed Web of Science ®Google Scholar
• Andersen G, Christrup LL, Sjogren P. (1997). Morphine metabolism-pharmacokinetics and pharmacodynamics. Ugeskr Laeger 159:3383–3386.
   PubMedGoogle Scholar
• Bachmann M, Schlatter C. (1981). Metabolism of [14C]emodin in the rat. Xenobiotica 11:217–225.
   PubMed Web of Science ®Google Scholar
• Badee J, Achour B, Rostami-Hodjegan A, Galetin A. (2015). Meta-analysis of expression of hepatic organic anion-transporting polypeptide (OATP) transporters in cellular systems relative to human liver tissue. Drug Metab Dispos 43:424–432.
   PubMed Web of Science ®Google Scholar
• Balistreri WF, Bezerra JA, Jansen P, et al. (2005). Intrahepatic cholestasis: Summary of an American Association for the Study of Liver Diseases single-topic conference. Hepatology 42:222–235.
   PubMed Web of Science ®Google Scholar
• Belinsky MG, Chen ZS, Shchaveleva I, et al. (2002). Characterization of the drug resistance and transport properties of multidrug resistance protein 6 (MRP6, ABCC6). Cancer Res 62:6172–6177.
   PubMed Web of Science ®Google Scholar
• Bera TK, Iavarone C, Kumar V, et al. (2002). MRP9, an unusual truncated member of the ABC transporter superfamily, is highly expressed in breast cancer. Proc Natl Acad Sci U S A 99:6997–7002.
   PubMed Web of Science ®Google Scholar
• Beyerle J, Frei E, Stiborova M, et al. (2015). Biotransformation of xenobiotics in the human colon and rectum and its association with colorectal cancer. Drug Metab Rev 47:199–221.
   PubMed Web of Science ®Google Scholar
• Biemans-Oldehinkel E, Doeven MK, Poolman B. (2006). ABC transporter architecture and regulatory roles of accessory domains. FEBS Lett 580:1023–1035.
   PubMed Web of Science ®Google Scholar
• Bloedon LT, Jeffcoat AR, Lopaczynski W, et al. (2002). Safety and pharmacokinetics of purified soy isoflavones: Single-dose administration to postmenopausal women. Am J Clin Nutr 76:1126–1137.
   PubMed Web of Science ®Google Scholar
• Bodo A, Bakos E, Szeri F, et al. (2003). Differential modulation of the human liver conjugate transporters MRP2 and MRP3 by bile acids and organic anions. J Biol Chem 278:23529–23537.
   PubMed Web of Science ®Google Scholar
• Borst P, Elferink RO. (2002). Mammalian ABC transporters in health and disease. Annu Rev Biochem 71:537–592.
   PubMed Web of Science ®Google Scholar
• Bortfeld M, Rius M, Konig J, et al. (2006). Human multidrug resistance protein 8 (MRP8/ABCC11), an apical efflux pump for steroid sulfates, is an axonal protein of the CNS and peripheral nervous system. Neuroscience 137:1247–1257.
   PubMed Web of Science ®Google Scholar
• Bosch TM. (2008). Pharmacogenomics of drug-metabolizing enzymes and drug transporters in chemotherapy. Methods Mol Biol 448:63–76.
   PubMedGoogle Scholar
• Brand W, van der Wel PA, Rein MJ, et al. (2008). Metabolism and transport of the citrus flavonoid hesperetin in Caco-2 cell monolayers. Drug Metab Dispos 36:1794–1802.
   PubMed Web of Science ®Google Scholar
• Buckley DB, Klaassen CD. (2007). Tissue- and gender-specific mRNA expression of UDP-glucuronosyltransferases (UGTs) in mice. Drug Metab Dispos 35:121–127.
   PubMed Web of Science ®Google Scholar
• Busby MG, Jeffcoat AR, Bloedon LT, et al. (2002). Clinical characteristics and pharmacokinetics of purified soy isoflavones: Single-dose administration to healthy men. Am J Clin Nutr 75:126–136.
   PubMed Web of Science ®Google Scholar
• Cai J, Gros P. (2003). Overexpression, purification, and functional characterization of ATP-binding cassette transporters in the yeast, Pichia pastoris. Biochim Biophys Acta 1610:63–76.
   PubMed Web of Science ®Google Scholar
• Chang JH, Uchizono JA, Park MS. (2011) Efflux of drugs via transporters—The antiabsorption pathway. In: Hu M, Li X, eds. Oral bioavailability: Basic principles, advanced concepts, and applications. New Jersey: Wiley, 111–126.
   Google Scholar
• Chen J, Lin H, Hu M. (2003a). Metabolism of flavonoids via enteric recycling: Role of intestinal disposition. J Pharmacol Exp Ther 304:1228–1235.
   PubMed Web of Science ®Google Scholar
• Chen J, Wang S, Jia X, et al. (2005a). Disposition of flavonoids via recycling: Comparison of intestinal versus hepatic disposition. Drug Metab Dispos 33:1777–1784.
   PubMed Web of Science ®Google Scholar
• Chen T, Li LP, Lu XY, et al. (2007). Absorption and excretion of luteolin and apigenin in rats after oral administration of Chrysanthemum morifolium extract. J Agric Food Chem 55:273–277.
   PubMed Web of Science ®Google Scholar
• Chen ZS, Guo Y, Belinsky MG, et al. (2005b). Transport of bile acids, sulfated steroids, estradiol 17-beta-d-glucuronide, and leukotriene C4 by human multidrug resistance protein 8 (ABCC11). Mol Pharmacol 67:545–557.
   PubMed Web of Science ®Google Scholar
• Chen ZS, Hopper-Borge E, Belinsky MG, et al. (2003b). Characterization of the transport properties of human multidrug resistance protein 7 (MRP7, ABCC10). Mol Pharmacol 63:351–358.
   PubMed Web of Science ®Google Scholar
• Chen ZS, Tiwari AK. (2011). Multidrug resistance proteins (MRPs/ABCCs) in cancer chemotherapy and genetic diseases. FEBS J 278:3226–3245.
   Google Scholar
• Cherrington NJ, Hartley DP, Li N, et al. (2002). Organ distribution of multidrug resistance proteins 1, 2, and 3 (Mrp1, 2, and 3) mRNA and hepatic induction of Mrp3 by constitutive androstane receptor activators in rats. J Pharmacol Exp Ther 300:97–104.
   PubMed Web of Science ®Google Scholar
• Christrup LL. (1997). Morphine metabolites. Acta Anaesthesiol Scand 41:116–122.
   PubMed Web of Science ®Google Scholar
• Collins DC, Balikian HM, Preedy JR. (1976). Splanchnic and intestinal uptake and formation of estriol and estriol conjugates in the dog in vivo. Steroids 28:597–612.
   PubMed Web of Science ®Google Scholar
• Court MH, Greenblatt DJ. (2000). Molecular genetic basis for deficient acetaminophen glucuronidation by cats: UGT1A6 is a pseudogene, and evidence for reduced diversity of expressed hepatic UGT1A isoforms. Pharmacogenetics 10:355–369.
   PubMedGoogle Scholar
• Crespy V, Nancoz N, Oliveira M, et al. (2004). Glucuronidation of the green tea catechins, (−)-epigallocatechin-3-gallate and (−)-epicatechin-3-gallate, by rat hepatic and intestinal microsomes. Free Radic Res 38:1025–1031.
   PubMed Web of Science ®Google Scholar
• Daali Y, Millet P, Dayer P, Pastor CM. (2013). Evidence of drug–drug interactions through uptake and efflux transport systems in rat hepatocytes: Implications for cellular concentrations of competing drugs. Drug Metab Dispos 41:1548–1556.
   PubMed Web of Science ®Google Scholar
• Dai P, Zhu L, Luo F, et al. (2015). Triple recycling processes impact systemic and local bioavailability of orally administered flavonoids. AAPS J 17:723–736.
   Google Scholar
• de Waart DR, Vlaming ML, Kunne C, et al. (2009). Complex pharmacokinetic behavior of ezetimibe depends on abcc2, abcc3, and abcg2. Drug Metab Dispos 37:1698–1702.
   PubMed Web of Science ®Google Scholar
• Dietrich CG, de Waart DR, Ottenhoff R, et al. (2001). Mrp2-deficiency in the rat impairs biliary and intestinal excretion and influences metabolism and disposition of the food-derived carcinogen 2-amino-1-methyl-6-phenylimidazo. Carcinogenesis 22:805–811.
   PubMed Web of Science ®Google Scholar
• Ding J, Chen X, Gao Z, et al. (2013). Metabolism and pharmacokinetics of novel selective vascular endothelial growth factor receptor-2 inhibitor apatinib in humans. Drug Metab Dispos 41:1195–1210.
   PubMed Web of Science ®Google Scholar
• Dowty ME, Lin J, Ryder TF, et al. (2014). The pharmacokinetics, metabolism, and clearance mechanisms of tofacitinib, a janus kinase inhibitor, in humans. Drug Metab Dispos 42:759–773.
   PubMed Web of Science ®Google Scholar
• Doyle L, Ross DD. (2003). Multidrug resistance mediated by the breast cancer resistance protein BCRP (ABCG2). Oncogene 22:7340–7358.
   PubMed Web of Science ®Google Scholar
• Dresser GK, Spence JD, Bailey DG. (2000). Pharmacokinetic–pharmacodynamic consequences and clinical relevance of cytochrome P450 3A4 inhibition. Clin Pharmacokinet 38:41–57.
   PubMed Web of Science ®Google Scholar
• Du J, Ma Z, Zhang Y, et al. (2014). Simultaneous determination of ornidazole and its main metabolites in human plasma by LC-MS/MS: Application to a pharmacokinetic study. Bioanalysis 6:2343–2356.
   PubMed Web of Science ®Google Scholar
• Du J, You T, Chen X, Zhong D. (2013). Stereoselective glucuronidation of ornidazole in humans: Predominant contribution of UDP-glucuronosyltransferases 1A9 and 2B7. Drug Metab Dispos 41:1306–1318.
   PubMed Web of Science ®Google Scholar
• El-Sheikh AA, Koenderink JB, Wouterse AC, et al. (2014). Renal glucuronidation and multidrug resistance protein 2-/ multidrug resistance protein 4-mediated efflux of mycophenolic acid: Interaction with cyclosporine and tacrolimus. Transl Res 164:46–56.
   PubMed Web of Science ®Google Scholar
• Emami Riedmaier A, Nies AT, Schaeffeler E, Schwab M. (2012). Organic anion transporters and their implications in pharmacotherapy. Pharmacol Rev 64:421–449.
   PubMed Web of Science ®Google Scholar
• Estudante M, Morais JG, Soveral G, Benet LZ. (2013). Intestinal drug transporters: An overview. Adv Drug Deliv Rev 65:1340–1356.
   PubMed Web of Science ®Google Scholar
• Ezzet F, Krishna G, Wexler DB, et al. (2001). A population pharmacokinetic model that describes multiple peaks due to enterohepatic recirculation of ezetimibe. Clin Ther 23:871–885.
   PubMed Web of Science ®Google Scholar
• Fahrmayr C, Fromm MF, Konig J. (2010). Hepatic OATP and OCT uptake transporters: Their role for drug–drug interactions and pharmacogenetic aspects. Drug Metab Rev 42:380–401.
   PubMed Web of Science ®Google Scholar
• Fedeniuk RW, Mizuno M, Neiser C, O'byrne C. (2015). Development of LC-MS/MS methodology for the detection/determination and confirmation of chloramphenicol, chloramphenicol 3-O-beta-d-glucuronide, florfenicol, florfenicol amine and thiamphenicol residues in bovine, equine and porcine liver. J Chromatogr B Analyt Technol Biomed Life Sci 991:68–78.
   PubMed Web of Science ®Google Scholar
• Fong SY, Wong YC, Zuo Z. (2014). Development of a SPE-LC/MS/MS method for simultaneous quantification of baicalein, wogonin, oroxylin A and their glucuronides baicalin, wogonoside and oroxyloside in rats and its application to brain uptake and plasma pharmacokinetic studies. J Pharm Biomed Anal 97:9–23.
   PubMed Web of Science ®Google Scholar
• Frances B, Gout R, Campistron G, et al. (1990). Morphine-6-glucuronide is more mu-selective and potent in analgesic tests than morphine. Prog Clin Biol Res 328:477–480.
   PubMedGoogle Scholar
• Frost J, Lokken TN, Brede WR, et al. (2015). A validated method for simultaneous determination of codeine, codeine-6-glucuronide, norcodeine, morphine, morphine-3-glucuronide and morphine-6-glucuronide in post-mortem blood, vitreous fluid, muscle, fat and brain tissue by LC-MS. J Anal Toxicol 39:203–212.
   PubMed Web of Science ®Google Scholar
• Fukuyama T, Yamaoka K, Ohata Y, Nakagawa T. (1994). A new analysis method for disposition kinetics of enterohepatic circulation of diclofenac in rats. Drug Metab Dispos 22:479–485.
   PubMed Web of Science ®Google Scholar
• Gao C, Zhang H, Guo Z, et al. (2012). Mechanistic studies on the absorption and disposition of scutellarin in humans: selective OATP2B1-mediated hepatic uptake is a likely key determinant for its unique pharmacokinetic characteristics. Drug Metab Dispos 40:2009–2020.
   PubMed Web of Science ®Google Scholar
• Gao S, Hu M. (2010). Bioavailability challenges associated with development of anti-cancer phenolics. Mini Rev Med Chem 10:550–567.
   PubMed Web of Science ®Google Scholar
• Gao S, Yang Z, Yin T, et al. (2011). Validated LC-MS/MS method for the determination of maackiain and its sulfate and glucuronide in blood: application to pharmacokinetic and disposition studies. J Pharm Biomed Anal 55:288–293.
   PubMed Web of Science ®Google Scholar
• Gao Y, Shao J, Jiang Z, et al. (2014). Drug enterohepatic circulation and disposition: Constituents of systems pharmacokinetics. Drug Discov Today 19:326–340.
   PubMed Web of Science ®Google Scholar
• Ge S, Gao S, Yin T, Hu M. (2015). Determination of pharmacokinetics of chrysin and its conjugates in wild-type FVB and Bcrp1 knockout mice using a validated LC-MS/MS method. J Agric Food Chem 63:2902–2910.
   PubMed Web of Science ®Google Scholar
• Ge S, Yin T, Xu B, et al. (2016). Curcumin affects phase II disposition of resveratrol through inhibiting efflux transporters MRP2 and BCRP. Pharm Res 33:590–602.
   PubMed Web of Science ®Google Scholar
• Ghosal A, Hapangama N, Yuan Y, et al. (2004). Identification of human UDP-glucuronosyltransferase enzyme(s) responsible for the glucuronidation of ezetimibe (Zetia). Drug Metab Dispos 32:314–320.
   PubMed Web of Science ®Google Scholar
• Ginsberg G, Guyton K, Johns D, et al. (2010). Genetic polymorphism in metabolism and host defense enzymes: Implications for human health risk assessment. Crit Rev Toxicol 40:575–619.
   PubMed Web of Science ®Google Scholar
• Glare PA, Walsh TD. (1991). Clinical pharmacokinetics of morphine. Ther Drug Monit 13:1–23.
   PubMed Web of Science ®Google Scholar
• Gong A, Chen X, Deng P, Zhong D. (2010). Metabolism of flumatinib, a novel antineoplastic tyrosine kinase inhibitor, in chronic myelogenous leukemia patients. Drug Metab Dispos 38:1328–1340.
   PubMed Web of Science ®Google Scholar
• Gradolatto A, Basly JP, Berges R, et al. (2005). Pharmacokinetics and metabolism of apigenin in female and male rats after a single oral administration. Drug Metab Dispos 33:49–54.
   PubMed Web of Science ®Google Scholar
• Grosser G, Doring B, Ugele B, et al. (2015). Transport of the soy isoflavone daidzein and its conjugative metabolites by the carriers SOAT, NTCP, OAT4, and OATP2B1. Arch Toxicol 89:2253–2263.
   PubMed Web of Science ®Google Scholar
• Gu D, Yang Y, Chen Q, et al. (2015). Identification of metabolites of rupestonic acid in rat urine by liquid chromatography combined with electrospray ionization quadrupole time-of-flight tandem mass spectrometry. Biomed Chromatogr 29:595–603.
   PubMed Web of Science ®Google Scholar
• Guillemette C. (2003). Pharmacogenomics of human UDP-glucuronosyltransferase enzymes. Pharmacogenomics J 3:136–158.
   PubMed Web of Science ®Google Scholar
• Guo L, Duan L, Dong X, et al. (2015). Metabolic profile of miltirone in rats by high performance liquid chromatography/quadrupole time-of-flight mass spectrometry. J Pharm Biomed Anal 107:473–479.
   PubMed Web of Science ®Google Scholar
• Hande K, Anthony L, Hamilton R, et al. (1988a). Identification of etoposide glucuronide as a major metabolite of etoposide in the rat and rabbit. Cancer Res 48:1829–1834.
   PubMed Web of Science ®Google Scholar
• Hande K, Bennett R, Hamilton R, et al. (1988b). Metabolism and excretion of etoposide in isolated, perfused rat liver models. Cancer Res 48:5692–5695.
   PubMed Web of Science ®Google Scholar
• Harding D, Fournel-Gigleux S, Jackson MR, Burchell B. (1988). Cloning and substrate specificity of a human phenol UDP-glucuronosyltransferase expressed in COS-7 cells. Proc Natl Acad Sci U S A 85:8381–8385.
   PubMed Web of Science ®Google Scholar
• Hattori M, Endo Y, Takebe S, et al. (1986). Metabolism of magnolol from Magnoliae cortex. II. Absorption, metabolism and excretion of [ring-14C]magnolol in rats. Chem Pharm Bull (Tokyo) 34:158–167.
   PubMed Web of Science ®Google Scholar
• Hirano H, Kurata A, Onishi Y, et al. (2006). High-speed screening and QSAR analysis of human ATP-binding cassette transporter ABCB11 (bile salt export pump) to predict drug-induced intrahepatic cholestasis. Mol Pharm 3:252–265.
   PubMed Web of Science ®Google Scholar
• Hirano M, Maeda K, Hayashi H, et al. (2005). Bile salt export pump (BSEP/ABCB11) can transport a nonbile acid substrate, pravastatin. J Pharmacol Exp Ther 314:876–882.
   PubMed Web of Science ®Google Scholar
• Hoffmann K, Loscher W. (2007). Upregulation of brain expression of P-glycoprotein in MRP2-deficient TR(−) rats resembles seizure-induced up-regulation of this drug efflux transporter in normal rats. Epilepsia 48:631–645.
   PubMed Web of Science ®Google Scholar
• Hollman PC, van Trijp JM, Mengelers MJ, et al. (1997). Bioavailability of the dietary antioxidant flavonol quercetin in man. Cancer Lett 114:139–140.
   PubMed Web of Science ®Google Scholar
• Hu M. (2007). Commentary: Bioavailability of flavonoids and polyphenols: Call to arms. Mol Pharm 4:803–806.
   PubMed Web of Science ®Google Scholar
• Hu M, Chen J, Lin H. (2003). Metabolism of flavonoids via enteric recycling: Mechanistic studies of disposition of apigenin in the Caco-2 cell culture model. J Pharmacol Exp Ther 307:314–321.
   PubMed Web of Science ®Google Scholar
• Itoh T, Takemoto I, Itagaki S, et al. (2004). Biliary excretion of irinotecan and its metabolites. J Pharm Pharm Sci 7:13–18.
   PubMed Web of Science ®Google Scholar
• Iusuf D, van de Steeg E, Schinkel AH. (2012). Hepatocyte hopping of OATP1B substrates contributes to efficient hepatic detoxification. Clin Pharmacol Ther 92:559–562.
   PubMed Web of Science ®Google Scholar
• Izukawa T, Nakajima M, Fujiwara R, et al. (2009). Quantitative analysis of UDP-glucuronosyltransferase (UGT) 1A and UGT2B expression levels in human livers. Drug Metab Dispos 37:1759–1768.
   PubMed Web of Science ®Google Scholar
• Jaganath IB, Mullen W, Edwards CA, Crozier A. (2006). The relative contribution of the small and large intestine to the absorption and metabolism of rutin in man. Free Radic Res 40:1035–1046.
   PubMed Web of Science ®Google Scholar
• Jager W, Gehring E, Hagenauer B, et al. (2003a). Biliary excretion of flavopiridol and its glucuronides in the isolated perfused rat liver: role of multidrug resistance protein 2 (Mrp2). Life Sci 73:2841–2854.
   PubMed Web of Science ®Google Scholar
• Jager W, Gehring E, Hagenauer B, et al. (2003b). The role of hepatic Mrp2 in the interaction of flavopiridol and bilirubin: Impact on therapy. Int J Clin Pharmacol Ther 41:610–611.
   PubMedGoogle Scholar
• James A, Blumenstein L, Glaenzel U, et al. (2015). Absorption, distribution, metabolism, and excretion of [(14)C]BYL719 (alpelisib) in healthy male volunteers. Cancer Chemother Pharmacol 76:751–760.
   PubMed Web of Science ®Google Scholar
• Jansen PL, Peters WH, Lamers WH. (1985). Hereditary chronic conjugated hyperbilirubinemia in mutant rats caused by defective hepatic anion transport. Hepatology 5:573–579.
   PubMed Web of Science ®Google Scholar
• Jemnitz K, Heredi-Szabo K, Janossy J, et al. (2010). ABCC2/Abcc2: A multispecific transporter with dominant excretory functions. Drug Metab Rev 42:402–436.
   PubMed Web of Science ®Google Scholar
• Jeong EJ, Jia X, Hu M. (2005a). Disposition of formononetin via enteric recycling: Metabolism and excretion in mouse intestinal perfusion and Caco-2 cell models. Mol Pharm 2:319–328.
   PubMed Web of Science ®Google Scholar
• Jeong EJ, Liu X, Jia X, et al. (2005b). Coupling of conjugating enzymes and efflux transporters: Impact on bioavailability and drug interactions. Curr Drug Metab 6:455–468.
   PubMed Web of Science ®Google Scholar
• Jia X, Chen J, Lin H, Hu M. (2004). Disposition of flavonoids via enteric recycling: Enzyme–transporter coupling affects metabolism of biochanin A and formononetin and excretion of their phase II conjugates. J Pharmacol Exp Ther 310:1103–1113.
   PubMed Web of Science ®Google Scholar
• Jiang W, Hu M. (2012). Mutual interactions between flavonoids and enzymatic and transporter elements responsible for flavonoid disposition via phase II metabolic pathways. RSC Adv 2:7948–7963.
   PubMed Web of Science ®Google Scholar
• Jiang W, Xu B, Wu B, et al. (2012). UDP-glucuronosyltransferase (UGT) 1A9-overexpressing HeLa cells is an appropriate tool to delineate the kinetic interplay between breast cancer resistance protein (BRCP) and UGT and to rapidly identify the glucuronide substrates of BCRP. Drug Metab Dispos 40:336–345.
   PubMed Web of Science ®Google Scholar
• Jirasko R, Holcapek M, Nobilis M. (2011). Identification of phase I and phase II metabolites of benfluron and dimefluron in rat urine using high-performance liquid chromatography/tandem mass spectrometry. Rapid Commun Mass Spectrom 25:2153–2162.
   PubMed Web of Science ®Google Scholar
• Johnson BM, Zhang P, Schuetz JD, Brouwer KL. (2006). Characterization of transport protein expression in multidrug resistance-associated protein (Mrp) 2-deficient rats. Drug Metab Dispos 34:556–562.
   PubMed Web of Science ®Google Scholar
• Jonker JW, Schinkel AH. (2004). Pharmacological and physiological functions of the polyspecific organic cation transporters: OCT1, 2, and 3 (SLC22A1-3). J Pharmacol Exp Ther 308:2–9.
   PubMed Web of Science ®Google Scholar
• Joy MS, Hilliard T, Hu Y, et al. (2009). Pharmacokinetics of mycophenolic acid in patients with lupus nephritis. Pharmacotherapy 29:7–16.
   PubMed Web of Science ®Google Scholar
• Kaivosaari S, Toivonen P, Hesse LM, et al. (2007). Nicotine glucuronidation and the human UDP-glucuronosyltransferase UGT2B10. Mol Pharmacol 72:761–768.
   PubMed Web of Science ®Google Scholar
• Kalliokoski A, Niemi M. (2009). Impact of OATP transporters on pharmacokinetics. Br J Pharmacol 158:693–705.
   PubMed Web of Science ®Google Scholar
• Kamdem LK, Liu Y, Stearns V, et al. (2010). In vitro and in vivo oxidative metabolism and glucuronidation of anastrozole. Br J Clin Pharmacol 70:854–869.
   PubMed Web of Science ®Google Scholar
• Kamisako T, Kobayashi Y, Takeuchi K, et al. (2000). Recent advances in bilirubin metabolism research: The molecular mechanism of hepatocyte bilirubin transport and its clinical relevance. J Gastroenterol 35:659–664.
   PubMed Web of Science ®Google Scholar
• Kamisako T, Leier I, Cui Y, et al. (1999). Transport of monoglucuronosyl and bisglucuronosyl bilirubin by recombinant human and rat multidrug resistance protein 2. Hepatology 30:485–490.
   PubMed Web of Science ®Google Scholar
• Kaneda N, Nagata H, Furuta T, Yokokura T. (1990). Metabolism and pharmacokinetics of the camptothecin analogue CPT-11 in the mouse. Cancer Res 50:1715–1720.
   PubMed Web of Science ®Google Scholar
• Kato A, Ueyama J, Abe F, et al. (2011). Panipenem does not alter the pharmacokinetics of the active metabolite of irinotecan SN-38 and inactive metabolite SN-38 glucuronide (SN-38G) in rats. Anticancer Res 31:2915–2922.
   PubMed Web of Science ®Google Scholar
• Kawai K, Kawasaki-Tokui Y, Odaka T, et al. (1997). Disposition and metabolism of the new oral antidiabetic drug troglitazone in rats, mice and dogs. Arzneimittelforschung 47:356–368.
   PubMed Web of Science ®Google Scholar
• Keppler D. (2011). Multidrug resistance proteins (MRPs, ABCCs): Importance for pathophysiology and drug therapy. Handb Exp Pharmacol 201:299–323.
   PubMedGoogle Scholar
• Keppler D. (2014). The roles of MRP2, MRP3, OATP1B1, and OATP1B3 in conjugated hyperbilirubinemia. Drug Metab Dispos 42:561–565.
   PubMed Web of Science ®Google Scholar
• Keppler D, Konig J. (1997). Hepatic canalicular membrane 5: Expression and localization of the conjugate export pump encoded by the MRP2 (cMRP/cMOAT) gene in liver. FASEB J 11:509–516.
   Google Scholar
• Keppler D, Konig J. (2000). Hepatic secretion of conjugated drugs and endogenous substances. Semin Liver Dis 20:265–272.
   PubMed Web of Science ®Google Scholar
• Kiang TK, Ensom MH, Chang TK. (2005). UDP-glucuronosyltransferases and clinical drug-drug interactions. Pharmacol Ther 106:97–132.
   PubMed Web of Science ®Google Scholar
• Kindla J, Fromm MF, Konig J. (2009). In vitro evidence for the role of OATP and OCT uptake transporters in drug-drug interactions. Expert Opin Drug Metab Toxicol 5:489–500.
   PubMed Web of Science ®Google Scholar
• King RA, Bursill DB. (1998). Plasma and urinary kinetics of the isoflavones daidzein and genistein after a single soy meal in humans. Am J Clin Nutr 67:867–872.
   PubMed Web of Science ®Google Scholar
• Kitamura Y, Kusuhara H, Sugiyama Y. (2010). Functional characterization of multidrug resistance-associated protein 3 (mrp3/abcc3) in the basolateral efflux of glucuronide conjugates in the mouse small intestine. J Pharmacol Exp Ther 332:659–666.
   PubMed Web of Science ®Google Scholar
• Klaassen CD, Aleksunes LM. (2010). Xenobiotic, bile acid, and cholesterol transporters: Function and regulation. Pharmacol Rev 62:1–96.
   PubMed Web of Science ®Google Scholar
• Kock K, Brouwer KL. (2012). A perspective on efflux transport proteins in the liver. Clin Pharmacol Ther 92:599–612.
   PubMed Web of Science ®Google Scholar
• Kool M, van der Linden M, de Haas M, et al. (1999). Expression of human MRP6, a homologue of the multidrug resistance protein gene MRP1, in tissues and cancer cells. Cancer Res 59:175–182.
   PubMed Web of Science ®Google Scholar
• Kosaka K, Sakai N, Endo Y, et al. (2011). Impact of intestinal glucuronidation on the pharmacokinetics of raloxifene. Drug Metab Dispos 39:1495–1502.
   PubMed Web of Science ®Google Scholar
• Kosoglou T, Statkevich P, Johnson-Levonas AO, et al. (2005). Ezetimibe: A review of its metabolism, pharmacokinetics and drug interactions. Clin Pharmacokinet 44:467–494.
   PubMed Web of Science ®Google Scholar
• Kouzuki H, Suzuki H, Ito K, et al. (1999). Contribution of organic anion transporting polypeptide to uptake of its possible substrates into rat hepatocytes. J Pharmacol Exp Ther 288:627–634.
   PubMed Web of Science ®Google Scholar
• Kruh GD, Belinsky MG. (2003). The MRP family of drug efflux pumps. Oncogene 22:7537–7522.
   PubMed Web of Science ®Google Scholar
• Kubo K, Sekine S, Saito M. (2009). Compensatory expression of MRP3 in the livers of MRP2-deficient EHBRs is promoted by DHA intake. Biosci Biotechnol Biochem 73:2432–2438.
   PubMed Web of Science ®Google Scholar
• Kuhnle G, Spencer JP, Schroeter H, et al. (2000). Epicatechin and catechin are O-methylated and glucuronidated in the small intestine. Biochem Biophys Res Commun 277:507–512.
   PubMed Web of Science ®Google Scholar
• Lagas JS, Sparidans RW, Wagenaar E, et al. (2010). Hepatic clearance of reactive glucuronide metabolites of diclofenac in the mouse is dependent on multiple ATP-binding cassette efflux transporters. Mol Pharmacol 77:687–694.
   PubMed Web of Science ®Google Scholar
• Lai MY, Hsiu SL, Chen CC, et al. (2003a). Urinary pharmacokinetics of baicalein, wogonin and their glycosides after oral administration of Scutellariae Radix in humans. Biol Pharm Bull 26:79–83.
   PubMed Web of Science ®Google Scholar
• Lai MY, Hsiu SL, Tsai SY, et al. (2003b). Comparison of metabolic pharmacokinetics of baicalin and baicalein in rats. J Pharm Pharmacol 55:205–209.
   PubMed Web of Science ®Google Scholar
• Lai YC, Kuo TF, Chen CK, et al. (2010). Metabolism of dicentrine: Identification of the phase I and phase II metabolites in miniature pig urine. Drug Metab Dispos 38:1714–1722.
   PubMed Web of Science ®Google Scholar
• Lakshmi VM, Hsu FF, Zenser TV. (2009). Identification of new 2-amino-3-methylimidazo[4,5-f]quinoline urinary metabolites from beta-naphthoflavone-treated mice. Drug Metab Dispos 37:1690–1697.
   PubMed Web of Science ®Google Scholar
• Laugesen S, Enggaard TP, Pedersen RS, et al. (2005). Paroxetine, a cytochrome P450 2D6 inhibitor, diminishes the stereoselective O-demethylation and reduces the hypoalgesic effect of tramadol. Clin Pharmacol Ther 77:312–323.
   PubMed Web of Science ®Google Scholar
• Li C, Homma M, Oka K. (1998). Characteristics of delayed excretion of flavonoids in human urine after administration of Shosaiko-to, a herbal medicine. Biol Pharm Bull 21:1251–1257.
   PubMed Web of Science ®Google Scholar
• Li Y, Zhou J, Ramsden D, et al. (2014). Enzyme–transporter interplay in the formation and clearance of abundant metabolites of faldaprevir found in excreta but not in circulation. Drug Metab Dispos 42:384–393.
   PubMed Web of Science ®Google Scholar
• Lin LC, Pai YF, Tsai TH. (2015). Isolation of luteolin and luteolin-7-O-glucoside from Dendranthema morifolium Ramat Tzvel and their pharmacokinetics in rats. J Agric Food Chem 63:7700–7706.
   PubMed Web of Science ®Google Scholar
• Liu GY, Wang W, Jia WD, et al. (2014). Protective effect of S-adenosylmethionine on hepatic ischemia-reperfusion injury during hepatectomy in HCC patients with chronic HBV infection. World J Surg Oncol 12:27.
   PubMed Web of Science ®Google Scholar
• Liu HX, Liu Y, Zhang JW, et al. (2008). UDP-glucuronosyltransferase 1A6 is the major isozyme responsible for protocatechuic aldehyde glucuronidation in human liver microsomes. Drug Metab Dispos 36:1562–1569.
   PubMed Web of Science ®Google Scholar
• Liu L, Cui Y, Chung AY, et al. (2006). Vectorial transport of enalapril by Oatp1a1/Mrp2 and OATP1B1 and OATP1B3/MRP2 in rat and human livers. J Pharmacol Exp Ther 318:395–402.
   PubMed Web of Science ®Google Scholar
• Liu W, Feng Q, Li Y, et al. (2012a). Coupling of UDP-glucuronosyltransferases and multidrug resistance-associated proteins is responsible for the intestinal disposition and poor bioavailability of emodin. Toxicol Appl Pharmacol 265:316–324.
   PubMed Web of Science ®Google Scholar
• Liu X, Li H, Bi KS, et al. (2012b). [Identification of metabolites of arbidol by ultra-high performance liquid chromatography tandem mass spectrometry]. Yao Xue Xue Bao 47:1521–1526.
   PubMedGoogle Scholar
• Liu Y, Hao H, Xie H, et al. (2009). Oxidative demethylenation and subsequent glucuronidation are the major metabolic pathways of berberine in rats. J Pharm Sci 98:4391–4401.
   PubMed Web of Science ®Google Scholar
• Liu Y, Liu Y, Dai Y, et al. (2003). Enteric disposition and recycling of flavonoids and ginkgo flavonoids. J Altern Complement Med 9:631–640.
   PubMed Web of Science ®Google Scholar
• Liu Z, Hu M. (2007). Natural polyphenol disposition via coupled metabolic pathways. Expert Opin Drug Metab Toxicol 3:389–406.
   PubMed Web of Science ®Google Scholar
• Lo MW, Pond SM, Effeney DJ, et al. (1984). Nonlinear formation of propranolol metabolites in dogs after portacaval transpositions. J Pharmacokinet Biopharm 12:401–412.
   PubMedGoogle Scholar
• LoGuidice A, Wallace BD, Bendel L, et al. (2012). Pharmacologic targeting of bacterial β-glucuronidase alleviates nonsteroidal anti-inflammatory drug-induced enteropathy in mice. J Pharmacol Exp Ther 341:447–454.
   PubMed Web of Science ®Google Scholar
• Loi CM, Young M, Randinitis E, et al. (1999). Clinical pharmacokinetics of troglitazone. Clin Pharmacokinet 37:91–104.
   PubMed Web of Science ®Google Scholar
• Lokiec F, Canal P, Gay C, et al. (1995). Pharmacokinetics of irinotecan and its metabolites in human blood, bile, and urine. Cancer Chemother Pharmacol 36:79–82.
   PubMed Web of Science ®Google Scholar
• Loureiro AI, Rocha JF, Fernandes-Lopes C, et al. (2014). Human disposition, metabolism and excretion of etamicastat, a reversible, peripherally selective dopamine β-hydroxylase inhibitor. Br J Clin Pharmacol 77:1017–1026.
   PubMed Web of Science ®Google Scholar
• Luo CF, Cai B, Hou N, et al. (2012). UDP-glucuronosyltransferase 1A1 is the principal enzyme responsible for puerarin metabolism in human liver microsomes. Arch Toxicol 86:1681–1690.
   PubMed Web of Science ®Google Scholar
• Luukkanen L, Taskinen J, Kurkela M, et al. (2005). Kinetic characterization of the 1A subfamily of recombinant human UDP-glucuronosyltransferases. Drug Metab Dispos 33:1017–1026.
   PubMed Web of Science ®Google Scholar
• Ma G, Lin J, Cai W, et al. (2014). Simultaneous determination of bilirubin and its glucuronides in liver microsomes and recombinant UGT1A1 enzyme incubation systems by HPLC method and its application to bilirubin glucuronidation studies. J Pharm Biomed Anal 92:149–159.
   PubMed Web of Science ®Google Scholar
• Ma L, Sun J, Peng Y, et al. (2012). Glucuronidation of edaravone by human liver and kidney microsomes: Biphasic kinetics and identification of UGT1A9 as the major UDP-glucuronosyltransferase isoform. Drug Metab Dispos 40:734–741.
   PubMed Web of Science ®Google Scholar
• Mackenzie PI, Bock KW, Burchell B, et al. (2005). Nomenclature update for the mammalian UDP glycosyltransferase (UGT) gene superfamily. Pharmacogenet Genomics 15:677–685.
   PubMed Web of Science ®Google Scholar
• Mackenzie PI, Gregory PA, Gardner-Stephen DA, et al. (2003). Regulation of UDP glucuronosyltransferase genes. Curr Drug Metab 4:249–257.
   PubMed Web of Science ®Google Scholar
• Madon J, Hagenbuch B, Landmann L, et al. (2000). Transport function and hepatocellular localization of mrp6 in rat liver. Mol Pharmacol 57:634–641.
   PubMed Web of Science ®Google Scholar
• Maier-Salamon A, Hagenauer B, Reznicek G, et al. (2008). Metabolism and disposition of resveratrol in the isolated perfused rat liver: Role of Mrp2 in the biliary excretion of glucuronides. J Pharm Sci 97:1615–1628.
   PubMed Web of Science ®Google Scholar
• Manach C, Morand C, Texier O, et al. (1995). Quercetin metabolites in plasma of rats fed diets containing rutin or quercetin. J Nutr 125:1911–1922.
   PubMed Web of Science ®Google Scholar
• Marin JJ. (2012). Plasma membrane transporters in modern liver pharmacology. Scientifica (Cairo) 2012:428139.
   PubMedGoogle Scholar
• Marquez B, Caceres NE, Mingeot-Leclercq MP, et al. (2009). Identification of the efflux transporter of the fluoroquinolone antibiotic ciprofloxacin in murine macrophages: studies with ciprofloxacin-resistant cells. Antimicrob Agents Chemother 53:2410–2416.
   PubMed Web of Science ®Google Scholar
• Marshall AW, Mihaly GW, Smallwood RA, et al. (1981). Fetal hepatic function: the disposition of propranolol in the pregnant sheep. Res Commun Chem Pathol Pharmacol 32:3–25.
   PubMedGoogle Scholar
• Matsunaga N, Wada S, Nakanishi T, et al. (2014). Mathematical modeling of the in vitro hepatic disposition of mycophenolic acid and its glucuronide in sandwich-cultured human hepatocytes. Mol Pharm 11:568–579.
   PubMed Web of Science ®Google Scholar
• Mazur CS, Marchitti SA, Dimova M, et al. (2012). Human and rat ABC transporter efflux of bisphenol a and bisphenol a glucuronide: interspecies comparison and implications for pharmacokinetic assessment. Toxicol Sci 128:317–325.
   PubMed Web of Science ®Google Scholar
• Meerman JH, Nijland C, Mulder GJ. (1987). Sex differences in sulfation and glucuronidation of phenol, 4-nitrophenol and N-hydroxy-2-acetylaminofluorene in the rat in vivo. Biochem Pharmacol 36:2605–2608.
   PubMed Web of Science ®Google Scholar
• Meng X, Maliakal P, Lu H, et al. (2004). Urinary and plasma levels of resveratrol and quercetin in humans, mice, and rats after ingestion of pure compounds and grape juice. J Agric Food Chem 52:935–942.
   PubMed Web of Science ®Google Scholar
• Meyer GM, Meyer MR, Wissenbach DK, Maurer HH. (2013). Studies on the metabolism and toxicological detection of glaucine, an isoquinoline alkaloid from Glaucium flavum (Papaveraceae), in rat urine using GC-MS, LC-MS(n) and LC-high-resolution MS(n). J Mass Spectrom 48:24–41.
   PubMed Web of Science ®Google Scholar
• Meyer MR, Holderbaum A, Kavanagh P, Maurer HH. (2015). Low resolution and high resolution MS for studies on the metabolism and toxicological detection of the new psychoactive substance methoxypiperamide (MeOP). J Mass Spectrom 50:1163–1174.
   PubMed Web of Science ®Google Scholar
• Meyer zu Schwabedissen HE, Kroemer HK. (2011). In vitro and in vivo evidence for the importance of breast cancer resistance protein transporters (BCRP/MXR/ABCP/ABCG2). Handb Exp Pharmacol201:325–371.
   PubMedGoogle Scholar
• Michels GM, Boudinot FD, Ferguson DC, Hoenig M. (2000). Pharmacokinetics of the insulin-sensitizing agent troglitazone in cats. Am J Vet Res 61:775–778.
   PubMed Web of Science ®Google Scholar
• Michely JA, Helfer AG, Brandt SD, et al. (2015). Metabolism of the new psychoactive substances N,N-diallyltryptamine (DALT) and 5-methoxy-DALT and their detectability in urine by GC-MS, LC-MSn, and LC-HR-MS-MS. Anal Bioanal Chem 407:7831–7842.
   PubMed Web of Science ®Google Scholar
• Ming X. (2008) Role of basolateral efflux transporters in intestinal absorption of drugs and prodrugs in: School of Pharmacy, pp 216, University of North Carolina at Chapel Hill Chapel Hill, North Carolina.
   Google Scholar
• Miyawaki I, Tamura A, Matsumoto I, et al. (2012). The effects of clobazam treatment in rats on the expression of genes and proteins encoding glucronosyltransferase 1A/2B (UGT1A/2B) and multidrug resistance-associated protein-2 (MRP2), and development of thyroid follicular cell hypertrophy. Toxicol Appl Pharmacol 265:351–359.
   PubMed Web of Science ®Google Scholar
• Miyazaki T, Mizukoshi H, Araki Y, Shimizu N. (1980). The metabolism of estriol-3-glucosiduronate and estriol in the rabbit. Endocrinol Jpn 27:175–182.
   PubMedGoogle Scholar
• Miyazaki T, Peric-Golia L, Slaunwhite WR Jr, Sandberg AA. (1972). Estriol metabolism in sheep: Excretion of biliary and urinary conjugates. Endocrinology 90:516–524.
   PubMed Web of Science ®Google Scholar
• Mizuno N, Takahashi T, Kusuhara H, et al. (2007). Evaluation of the role of breast cancer resistance protein (BCRP/ABCG2) and multidrug resistance-associated protein 4 (MRP4/ABCC4) in the urinary excretion of sulfate and glucuronide metabolites of edaravone (MCI-186; 3-methyl-1-phenyl-2-pyrazolin-5-one). Drug Metab Dispos 35:2045–2052.
   PubMed Web of Science ®Google Scholar
• Moon YJ, Morris ME. (2007). Pharmacokinetics and bioavailability of the bioflavonoid biochanin A: Effects of quercetin and EGCG on biochanin A disposition in rats. Mol Pharm 4:865–872.
   PubMed Web of Science ®Google Scholar
• Morand C, Crespy V, Manach C, et al. (1998). Plasma metabolites of quercetin and their antioxidant properties. Am J Physiol 275:R212–R219.
   PubMed Web of Science ®Google Scholar
• Morikawa A, Goto Y, Suzuki H, et al. (2000). Biliary excretion of 17beta-estradiol 17beta-d-glucuronide is predominantly mediated by cMOAT/MRP2. Pharm Res 17:546–552.
   PubMed Web of Science ®Google Scholar
• Motheova O, Bezek S, Durisova M, et al. (1986). The pharmacokinetics of exaprolol and propranolol in rats with interrupted enterohepatic circulation. Biopharm Drug Dispos 7:151–162.
   PubMed Web of Science ®Google Scholar
• Musey PI, Kirdani RY, Bhanalaph T, Sandberg AA. (1973). Estriol metabolism in the baboon: Analysis of urinary and biliary metabolites. Steroids 22:795–817.
   PubMed Web of Science ®Google Scholar
• Nadal T, Ortuno J, Pascual JA. (1996). Rapid and sensitive determination of zidovudine and zidovudine glucuronide in human plasma by ion-pair high-performance liquid chromatography. J Chromatogr A 721:127–137.
   PubMed Web of Science ®Google Scholar
• Naesens M, de Loor H, Vanrenterghem Y, Kuypers DR. (2007). The impact of renal allograft function on exposure and elimination of mycophenolic acid (MPA) and its metabolite MPA 7-O-glucuronide. Transplantation 84:362–373.
   PubMed Web of Science ®Google Scholar
• Nagar S, Blanchard RL. (2006). Pharmacogenetics of uridine diphosphoglucuronosyltransferase (UGT) 1A family members and its role in patient response to irinotecan. Drug Metab Rev 38:393–409.
   PubMed Web of Science ®Google Scholar
• Nagar S, Remmel RP. (2006). Uridine diphosphoglucuronosyltransferase pharmacogenetics and cancer. Oncogene 25:1659–1672.
   PubMed Web of Science ®Google Scholar
• Nakagomi-Hagihara R, Nakai D, Tokui T. (2007a). Inhibition of human organic anion transporter 3 mediated pravastatin transport by gemfibrozil and the metabolites in humans. Xenobiotica 37:416–426.
   PubMed Web of Science ®Google Scholar
• Nakagomi-Hagihara R, Nakai D, Tokui T, et al. (2007b). Gemfibrozil and its glucuronide inhibit the hepatic uptake of pravastatin mediated by OATP1B1. Xenobiotica 37:474–486.
   PubMed Web of Science ®Google Scholar
• Nakanishi T, Ross DD. (2012). Breast cancer resistance protein (BCRP/ABCG2): Its role in multidrug resistance and regulation of its gene expression. Chin J Cancer 31:73–99.
   PubMed Web of Science ®Google Scholar
• Nakazawa T, Yasuda T, Ohsawa K. (2003). Metabolites of orally administered Magnolia officinalis extract in rats and man and its antidepressant-like effects in mice. J Pharm Pharmacol 55:1583–1591.
   PubMed Web of Science ®Google Scholar
• Nambara T, Kawarada Y. (1977). Biliary conjugated metabolites of estriol in the rat. Chem Pharm Bull (Tokyo) 25:942–948.
   PubMed Web of Science ®Google Scholar
• Neve EP, Artursson P, Ingelman-Sundberg M, Karlgren M. (2013). An integrated in vitro model for simultaneous assessment of drug uptake, metabolism, and efflux. Mol Pharm 10:3152–3163.
   PubMed Web of Science ®Google Scholar
• Ni ZL, Bikadi Z, Rosenberg MF, Mao QC. (2010). Structure and function of the human breast cancer resistance protein (BCRP/ABCG2). Curr Drug Metab 11:603–617.
   PubMed Web of Science ®Google Scholar
• Nies AT, Jedlitschky G, Konig J, et al. (2004). Expression and immunolocalization of the multidrug resistance proteins, MRP1-MRP6 (ABCC1-ABCC6), in human brain. Neuroscience 129:349–360.
   PubMed Web of Science ®Google Scholar
• Nies AT, Schwab M, Keppler D. (2008). Interplay of conjugating enzymes with OATP uptake transporters and ABCC/MRP efflux pumps in the elimination of drugs. Expert Opin Drug Metab Toxicol 4:545–568.
   PubMed Web of Science ®Google Scholar
• Ohno S, Nakajin S. (2009). Determination of mRNA expression of human UDP-glucuronosyltransferases and application for localization in various human tissues by real-time reverse transcriptase-polymerase chain reaction. Drug Metab Dispos 37:32–40.
   PubMed Web of Science ®Google Scholar
• Ohtsuki S, Schaefer O, Kawakami H, et al. (2012). Simultaneous absolute protein quantification of transporters, cytochromes P450, and UDP-glucuronosyltransferases as a novel approach for the characterization of individual human liver: comparison with mRNA levels and activities. Drug Metab Dispos 40:83–92.
   PubMed Web of Science ®Google Scholar
• Osborne R, Joel S, Grebenik K, et al. (1993). The pharmacokinetics of morphine and morphine glucuronides in kidney failure. Clin Pharmacol Ther 54:158–167.
   PubMed Web of Science ®Google Scholar
• Oswald S, Koll C, Siegmund W. (2007). Disposition of the cholesterol absorption inhibitor ezetimibe in mdr1a/b (-/-) mice. J Pharm Sci 96:3478–3484.
   PubMed Web of Science ®Google Scholar
• Oswald S, Konig J, Lutjohann D, et al. (2008). Disposition of ezetimibe is influenced by polymorphisms of the hepatic uptake carrier OATP1B1. Pharmacogenet Genomics 18:559–568.
   PubMed Web of Science ®Google Scholar
• Oswald S, May K, Rosin J, et al. (2010). Synergistic influence of Abcb1 and Abcc2 on disposition and sterol lowering effects of ezetimibe in rats. J Pharm Sci 99:422–429.
   PubMed Web of Science ®Google Scholar
• Ouellet DM, Pollack GM. (1995). Biliary excretion and enterohepatic recirculation of morphine-3-glucuronide in rats. Drug Metab Dispos 23:478–484.
   PubMed Web of Science ®Google Scholar
• Owens IS, Basu NK, Banerjee R. (2005). UDP-glucuronosyltransferases: Gene structures of UGT1 and UGT2 families. Meth Enzymol 400:1–22.
   PubMed Web of Science ®Google Scholar
• Pan S, Neeraj A, Srivastava KS, et al. (2013). A proposal for a quality system for herbal products. J Pharm Sci 102:4230–4241.
   PubMed Web of Science ®Google Scholar
• Pang KS, Maeng HJ, Fan J. (2009). Interplay of transporters and enzymes in drug and metabolite processing. Mol Pharm 6:1734–1755.
   PubMed Web of Science ®Google Scholar
• Peng HW, Huang YT, Chen CF, Tsai TH. (1998). Glucuronidation of naringenin in rats. Planta Med 64:779.
   PubMed Web of Science ®Google Scholar
• Peng KW, Bacon J, Zheng M, et al. (2015). Ethnic variability in the expression of hepatic drug transporters: Absolute quantification by an optimized targeted quantitative proteomic approach. Drug Metab Dispos 43:1045–1055.
   PubMed Web of Science ®Google Scholar
• Perera MA, Innocenti F, Ratain MJ. (2008). Pharmacogenetic testing for uridine diphosphate glucuronosyltransferase 1A1 polymorphisms: Are we there yet? Pharmacotherapy 28:755–768.
   PubMed Web of Science ®Google Scholar
• Pfeifer ND, Hardwick RN, Brouwer KL. (2014). Role of hepatic efflux transporters in regulating systemic and hepatocyte exposure to xenobiotics. Annu Rev Pharmacol Toxicol 54:509–535.
   PubMed Web of Science ®Google Scholar
• Phillips IR, Shephard EA, Povey S, et al. (1985). A cytochrome P-450 gene family mapped to human chromosome 19. Ann Hum Genet 49:267–274.
   PubMed Web of Science ®Google Scholar
• Pogell BM, Leloir LF. (1961). Nucleotide activation of liver microsomal glucuronidation. J Biol Chem 236:293–298.
   PubMed Web of Science ®Google Scholar
• Qian MR, Zeng S. (2006). Biosynthesis of imipramine glucuronide and characterization of imipramine glucuronidation catalyzed by recombinant UGT1A4. Acta Pharmacol Sin 27:623–628.
   PubMed Web of Science ®Google Scholar
• Radominska-Pandya A, Bratton SM, Redinbo MR, Miley MJ. (2010). The crystal structure of human UDP-glucuronosyltransferase 2B7 C-terminal end is the first mammalian UGT target to be revealed: The significance for human UGTs from both the 1A and 2B families. Drug Metab Rev 42:133–144.
   PubMed Web of Science ®Google Scholar
• Radominska-Pandya A, Little JM, Pandya JT, et al. (1998). UDP-glucuronosyltransferases in human intestinal mucosa. Biochim Biophys Acta 1394:199–208.
   PubMed Web of Science ®Google Scholar
• Ramanathan R, Reyderman L, Kulmatycki K, et al. (2007). Disposition of loratadine in healthy volunteers. Xenobiotica 37:753–769.
   PubMed Web of Science ®Google Scholar
• Redmon JM, Shrestha B, Cerundolo R, Court MH. (2016). Soy isoflavone metabolism in cats compared with other species: Urinary metabolite concentrations and glucuronidation by liver microsomes. Xenobiotica 46:406–415.
   PubMed Web of Science ®Google Scholar
• Reynolds JW. (1966). 16-Alpha-hydroxylation of pregnenolone by human liver. Steroids 7:261–271.
   PubMed Web of Science ®Google Scholar
• Roberts MS, Magnusson BM, Burczynski FJ, Weiss M. (2002). Enterohepatic circulation: Physiological, pharmacokinetic and clinical implications. Clin Pharmacokinet 41:751–790.
   PubMed Web of Science ®Google Scholar
• Roth M, Obaidat A, Hagenbuch B. (2012). OATPs, OATs and OCTs: The organic anion and cation transporters of the SLCO and SLC22A gene superfamilies. Br J Pharmacol 165:1260–1287.
   PubMed Web of Science ®Google Scholar
• Routledge PA, Shand DG. (1979). Clinical pharmacokinetics of propranolol. Clin Pharmacokinet 4:73–90.
   PubMed Web of Science ®Google Scholar
• Rowland A, Mackenzie PI, Miners JO. (2015). Transporter-mediated uptake of UDP-glucuronic acid by human liver microsomes: Assay conditions, kinetics, and inhibition. Drug Metab Dispos 43:147–153.
   PubMed Web of Science ®Google Scholar
• Russel FG, Koenderink JB, Masereeuw R. (2008). Multidrug resistance protein 4 (MRP4/ABCC4): A versatile efflux transporter for drugs and signalling molecules. Trends Pharmacol Sci 29:200–207.
   PubMed Web of Science ®Google Scholar
• Sasabe H, Tsuji A, Sugiyama Y. (1998). Carrier-mediated mechanism for the biliary excretion of the quinolone antibiotic grepafloxacin and its glucuronide in rats. J Pharmacol Exp Ther 284:1033–1039.
   PubMed Web of Science ®Google Scholar
• Schaiquevich P, Niselman A, Rubio M. (2002). Comparison of two compartmental models for describing ranitidine's plasmatic profiles. Pharmacol Res 45:399–405.
   PubMed Web of Science ®Google Scholar
• Schwartz DE, Jordan JC, Vetter W, Oesterhelt G. (1979). Metabolic studies of ornidazole in the rat, in the dog and in man. Xenobiotica 9:571–581.
   PubMed Web of Science ®Google Scholar
• Seitz S, Boelsterli UA. (1998). Diclofenac acyl glucuronide, a major biliary metabolite, is directly involved in small intestinal injury in rats. Gastroenterology 115:1476–1482.
   PubMed Web of Science ®Google Scholar
• Shelby MK, Cherrington NJ, Vansell NR, Klaassen CD. (2003). Tissue mRNA expression of the rat UDP-glucuronosyltransferase gene family. Drug Metab Dispos 31:326–333.
   PubMed Web of Science ®Google Scholar
• Shi J, Zheng L, Lin Z, et al. (2015). Study of pharmacokinetic profiles and characteristics of active components and their metabolites in rat plasma following oral administration of the water extract of Astragali radix using UPLC-MS/MS. J Ethnopharmacol 169:183–194.
   PubMed Web of Science ®Google Scholar
• Shi S, Li Y. (2014). Interplay of drug-metabolizing enzymes and transporters in drug absorption and disposition. Curr Drug Metab 15:915–941.
   PubMed Web of Science ®Google Scholar
• Shia CS, Hou YC, Tsai SY, et al. (2010). Differences in pharmacokinetics and ex vivo antioxidant activity following intravenous and oral administrations of emodin to rats. J Pharm Sci 99:2185–2195.
   PubMed Web of Science ®Google Scholar
• Shimoi K, Okada H, Furugori M, et al. (1998). Intestinal absorption of luteolin and luteolin 7-O-beta-glucoside in rats and humans. FEBS Lett 438:220–224.
   PubMed Web of Science ®Google Scholar
• Shipkova M, Armstrong VW, Oellerich M, Wieland E. (2003). Acyl glucuronide drug metabolites: Toxicological and analytical implications. Ther Drug Monit 25:1–16.
   PubMed Web of Science ®Google Scholar
• Silberberg M, Morand C, Mathevon T, et al. (2006). The bioavailability of polyphenols is highly governed by the capacity of the intestine and of the liver to secrete conjugated metabolites. Eur J Nutr 45:88–96.
   PubMed Web of Science ®Google Scholar
• Singh R, Hu M. (2011). Drug metabolism in gastrointestinal tract. In: Hu M, Li X, eds. Oral bioavailability: Basic principles, advanced concepts, and applications. New Jersey: Wiley, 91–109.
   Google Scholar
• Singh R, Wu B, Tang L, Hu M. (2011a). Uridine diphosphate glucuronosyltransferase isoform-dependent regiospecificity of glucuronidation of flavonoids. J Agric Food Chem 59:7452–7464.
   PubMed Web of Science ®Google Scholar
• Singh SP, Wahajuddin Tewari D, et al. (2011b). PAMPA permeability, plasma protein binding, blood partition, pharmacokinetics and metabolism of formononetin, a methoxylated isoflavone. Food Chem Toxicol 49:1056–1062.
   PubMed Web of Science ®Google Scholar
• Song YL, Jing WH, Yan R, Wang YT. (2014). Metabolic characterization of (±)-praeruptorin A in vitro and in vivo by high performance liquid chromatography coupled with hybrid triple quadrupole-linear ion trap mass spectrometry and time-of-flight mass spectrometry. J Pharm Biomed Anal 90:98–110.
   PubMed Web of Science ®Google Scholar
• Stearns V, Johnson MD, Rae JM, et al. (2003). Active tamoxifen metabolite plasma concentrations after coadministration of tamoxifen and the selective serotonin reuptake inhibitor paroxetine. J Natl Cancer Inst 95:1758–1764.
   PubMed Web of Science ®Google Scholar
• Stephanson N, Dahl H, Helander A, Beck O. (2005). Determination of urinary 5-hydroxytryptophol glucuronide by liquid chromatography-mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci 816:107–112.
   PubMed Web of Science ®Google Scholar
• Stone AN, Mackenzie PI, Galetin A, et al. (2003). Isoform selectivity and kinetics of morphine 3- and 6-glucuronidation by human udp-glucuronosyltransferases: Evidence for atypical glucuronidation kinetics by UGT2B7. Drug Metab Dispos 31:1086–1089.
   PubMed Web of Science ®Google Scholar
• Stopfer P, Rathgen K, Bischoff D, et al. (2011). Pharmacokinetics and metabolism of BIBF 1120 after oral dosing to healthy male volunteers. Xenobiotica 41:297–311.
   PubMed Web of Science ®Google Scholar
• Talbi A, Zhao D, Liu Q, et al. (2014). Pharmacokinetics, tissue distribution, excretion and plasma protein binding studies of wogonin in rats. Molecules 19:5538–5549.
   PubMed Web of Science ®Google Scholar
• Tan EY, Hartmann G, Chen Q, et al. (2010). Pharmacokinetics, metabolism, and excretion of anacetrapib, a novel inhibitor of the cholesteryl ester transfer protein, in rats and rhesus monkeys. Drug Metab Dispos 38:459–473.
   PubMed Web of Science ®Google Scholar
• Tang L, Li Y, Chen WY, et al. (2014). Breast cancer resistance protein-mediated efflux of luteolin glucuronides in HeLa cells overexpressing UDP-glucuronosyltransferase 1A9. Pharm Res 31:847–860.
   PubMed Web of Science ®Google Scholar
• Thilakarathna SH, Rupasinghe HP. (2013). Flavonoid bioavailability and attempts for bioavailability enhancement. Nutrients 5:3367–3387.
   PubMed Web of Science ®Google Scholar
• Tian JX, Wang M, Xu L, et al. (2014). Metabolism of brucine: The important metabolic pathways of dihydroindole-type alkaloid for excretion in rats. Bioanalysis 6:137–149.
   PubMed Web of Science ®Google Scholar
• Tian S, He G, Song J, et al. (2012). Pharmacokinetic study of baicalein after oral administration in monkeys. Fitoterapia 83:532–540.
   PubMed Web of Science ®Google Scholar
• Tian X, Swift B, Zamek-Gliszczynski MJ, et al. (2008). Impact of basolateral multidrug resistance-associated protein (Mrp) 3 and Mrp4 on the hepatobiliary disposition of fexofenadine in perfused mouse livers. Drug Metab Dispos 36:911–915.
   PubMed Web of Science ®Google Scholar
• Tong Z, Chandrasekaran A, DeMaio W, et al. (2010). Metabolism of vabicaserin in mice, rats, dogs, monkeys, and humans. Drug Metab Dispos 38:2266–2277.
   PubMed Web of Science ®Google Scholar
• Town C, Henderson L, Chang D, et al. (1993). Distribution of 1-aminobenzotriazole in male rats after administration of an oral dose. Xenobiotica 23:383–390.
   PubMed Web of Science ®Google Scholar
• Trdan T, Roskar R, Trontelj J, et al. (2011). Determination of raloxifene and its glucuronides in human urine by liquid chromatography-tandem mass spectrometry assay. J Chromatogr B Analyt Technol Biomed Life Sci 879:2323–2331.
   PubMed Web of Science ®Google Scholar
• Tukey RH, Strassburg CP. (2000). Human UDP-glucuronosyltransferases: Metabolism, expression, and disease. Annu Rev Pharmacol Toxicol 40:581–616.
   PubMed Web of Science ®Google Scholar
• Uchaipichat V, Mackenzie PI, Elliot DJ, Miners JO. (2006). Selectivity of substrate (trifluoperazine) and inhibitor (amitriptyline, androsterone, canrenoic acid, hecogenin, phenylbutazone, quinidine, quinine, and sulfinpyrazone) “‘probes’ for human udpglucuronosyltransferases” . Drug Metab Dispos 34:449–456.
   PubMed Web of Science ®Google Scholar
• Uutela P, Karhu L, Piepponen P, et al. (2009). Discovery of dopamine glucuronide in rat and mouse brain microdialysis samples using liquid chromatography tandem mass spectrometry. Anal Chem 81:427–434.
   PubMed Web of Science ®Google Scholar
• Uwai Y, Motohashi H, Tsuji Y, et al. (2007). Interaction and transport characteristics of mycophenolic acid and its glucuronide via human organic anion transporters hOAT1 and hOAT3. Biochem Pharmacol 74:161–168.
   PubMed Web of Science ®Google Scholar
• Vaidyanathan JB, Walle T. (2002). Glucuronidation and sulfation of the tea flavonoid (−)-epicatechin by the human and rat enzymes. Drug Metab Dispos 30:897–903.
   PubMed Web of Science ®Google Scholar
• van de Steeg E, Stranecky V, Hartmannova H, et al. (2012). Complete OATP1B1 and OATP1B3 deficiency causes human Rotor syndrome by interrupting conjugated bilirubin reuptake into the liver. J Clin Invest 122:519–528.
   PubMed Web of Science ®Google Scholar
• van de Steeg E, Wagenaar E, van der Kruijssen CM, et al. (2010). Organic anion transporting polypeptide 1a/1b-knockout mice provide insights into hepatic handling of bilirubin, bile acids, and drugs. J Clin Invest 120:2942–2952.
   PubMed Web of Science ®Google Scholar
• van de Wetering K, Burkon A, Feddema W, et al. (2009). Intestinal breast cancer resistance protein (BCRP)/Bcrp1 and multidrug resistance protein 3 (MRP3)/Mrp3 are involved in the pharmacokinetics of resveratrol. Mol Pharmacol 75:876–885.
   PubMed Web of Science ®Google Scholar
• van Den Elsen JM, Kuntz DA, Hoedemaeker FJ, Rose DR. (1999). Antibody C219 recognizes an alpha-helical epitope on P-glycoprotein. Proc Natl Acad Sci USA 96:13679–13684.
   PubMed Web of Science ®Google Scholar
• van der Deen M, de Vries EG, Timens W, et al. (2005). ATP-binding cassette (ABC) transporters in normal and pathological lung. Respir Res 6:59.
   PubMed Web of Science ®Google Scholar
• Vasilyeva A, Durmus S, Li L, et al. (2015). Hepatocellular shuttling and recirculation of sorafenib-glucuronide is dependent on Abcc2, Abcc3, and Oatp1a/1b. Cancer Res 75:2729–2736.
   PubMed Web of Science ®Google Scholar
• Villanueva SS, Ruiz ML, Ghanem CI, et al. (2008). Hepatic synthesis and urinary elimination of acetaminophen glucuronide are exacerbated in bile duct-ligated rats. Drug Metab Dispos 36:475–480.
   PubMed Web of Science ®Google Scholar
• Wakabayashi Y, Lippincott-Schwartz J, Arias IM. (2004). Intracellular trafficking of bile salt export pump (ABCB11) in polarized hepatic cells: Constitutive cycling between the canalicular membrane and rab11-positive endosomes. Mol Biol Cell 15:3485–3496.
   PubMed Web of Science ®Google Scholar
• Wallace BD, Wang H, Lane KT, et al. (2010). Alleviating cancer drug toxicity by inhibiting a bacterial enzyme. Science 330:831–835.
   PubMed Web of Science ®Google Scholar
• Walle T, Hsieh F, DeLegge MH, et al. (2004). High absorption but very low bioavailability of oral resveratrol in humans. Drug Metab Dispos 32:1377–1382.
   PubMed Web of Science ®Google Scholar
• Walle T, Otake Y, Brubaker JA, et al. (2001). Disposition and metabolism of the flavonoid chrysin in normal volunteers. Br J Clin Pharmacol 51:143–146.
   PubMed Web of Science ®Google Scholar
• Walle T, Walle UK, Olanoff LS. (1985). Quantitative account of propranolol metabolism in urine of normal man. Drug Metab Dispos 13:204–209.
   PubMed Web of Science ®Google Scholar
• Wang H, Fang ZZ, Zheng Y, et al. (2014). Metabolic profiling of praziquantel enantiomers. Biochem Pharmacol 90:166–178.
   PubMed Web of Science ®Google Scholar
• Wang M, Yang G, He Y, et al. (2016). Establishment and use of new MDCK II cells overexpressing both UGT1A1 and MRP2 to characterize flavonoid metabolism via the glucuronidation pathway. Mol Nutr Food Res 60:1967–1983.
   PubMed Web of Science ®Google Scholar
• Wang SW, Chen J, Jia X, et al. (2006). Disposition of flavonoids via enteric recycling: structural effects and lack of correlations between in vitro and in situ metabolic properties. Drug Metab Dispos 34:1837–1848.
   PubMed Web of Science ®Google Scholar
• Wang SW, Kulkarni KH, Tang L, et al. (2009). Disposition of flavonoids via enteric recycling: UDP-glucuronosyltransferase (UGT) 1As deficiency in Gunn rats is compensated by increases in UGT2Bs activities. J Pharmacol Exp Ther 329:1023–1031.
   PubMed Web of Science ®Google Scholar
• Wei Y, Wu B, Jiang W, et al. (2013). Revolving door action of breast cancer resistance protein (BCRP) facilitates or controls the efflux of flavone glucuronides from UGT1A9-overexpressing HeLa cells. Mol Pharm 10:1736–1750.
   PubMed Web of Science ®Google Scholar
• Welter J, Meyer MR, Kavanagh P, Maurer HH. (2014). Studies on the metabolism and the detectability of 4-methyl-amphetamine and its isomers 2-methyl-amphetamine and 3-methyl-amphetamine in rat urine using GC-MS and LC-(high-resolution)-MSn. Anal Bioanal Chem 406:1957–1974.
   PubMed Web of Science ®Google Scholar
• Wen Z, Tallman MN, Ali SY, Smith PC. (2007). UDP-glucuronosyltransferase 1A1 is the principal enzyme responsible for etoposide glucuronidation in human liver and intestinal microsomes: Structural characterization of phenolic and alcoholic glucuronides of etoposide and estimation of enzyme kinetics. Drug Metab Dispos 35:371–380.
   PubMed Web of Science ®Google Scholar
• Westley IS, Brogan LR, Morris RG, et al. (2006). Role of Mrp2 in the hepatic disposition of mycophenolic acid and its glucuronide metabolites: Effect of cyclosporine. Drug Metab Dispos 34:261–266.
   PubMed Web of Science ®Google Scholar
• Williams JA, Hyland R, Jones BC, et al. (2004). Drug-drug interactions for UDP-glucuronosyltransferase substrates: A pharmacokinetic explanation for typically observed low exposure (AUCi/AUC) ratios. Drug Metab Dispos 32:1201–1208.
   PubMed Web of Science ®Google Scholar
• Wink CS, Meyer MR, Braun T, et al. (2015). Biotransformation and detectability of the designer drug 2,5-dimethoxy-4-propylphenethylamine (2C-P) studied in urine by GC-MS, LC-MS(n), and LC-high-resolution-MS(n). Anal Bioanal Chem 407:831–843.
   PubMed Web of Science ®Google Scholar
• Wittgen HG, van den Heuvel JJ, van den Broek PH, et al. (2012). Transport of the coumarin metabolite 7-hydroxycoumarin glucuronide is mediated via multidrug resistance-associated proteins 3 and 4. Drug Metab Dispos 40:1076–1079.
   PubMed Web of Science ®Google Scholar
• Wolff T, Samuelsson H, Hedner T. (1995). Morphine and morphine metabolite concentrations in cerebrospinal fluid and plasma in cancer pain patients after slow-release oral morphine administration. Pain 62:147–154.
   PubMed Web of Science ®Google Scholar
• Wong CC, Barron D, Orfila C, et al. (2011). Interaction of hydroxycinnamic acids and their conjugates with organic anion transporters and ATP-binding cassette transporters. Mol Nutr Food Res 55:979–988.
   PubMed Web of Science ®Google Scholar
• Wu B. (2012). Pharmacokinetic interplay of phase II metabolism and transport: A theoretical study. J Pharm Sci 101:381–393.
   PubMed Web of Science ®Google Scholar
• Wu B, Dong D, Hu M, Zhang S. (2013). Quantitative prediction of glucuronidation in humans using the in vitro–in vivo extrapolation approach. Curr Top Med Chem 13:1343–1352.
   PubMed Web of Science ®Google Scholar
• Wu W, Hu N, Zhang Q, et al. (2014). In vitro glucuronidation of five rhubarb anthraquinones by intestinal and liver microsomes from humans and rats. Chem Biol Interact 219:18–27.
   PubMed Web of Science ®Google Scholar
• Wu WN, McKown LA, Reitz AB. (2007). Metabolic fate of the antipsychotic agent, mazapertine, in man-API-MS and MS/MS identification of urinary metabolites . Eur J Drug Metab Pharmacokinet 32:171–176.
   PubMed Web of Science ®Google Scholar
• Xia B, Zhou Q, Zheng Z, et al. (2012). A novel local recycling mechanism that enhances enteric bioavailability of flavonoids and prolongs their residence time in the gut. Mol Pharm 9:3246–3258.
   PubMed Web of Science ®Google Scholar
• Xu B, Yang G, Ge S, et al. (2013). Validated LC-MS/MS method for the determination of 3-hydroxflavone and its glucuronide in blood and bioequivalent buffers: application to pharmacokinetic, absorption, and metabolism studies. J Pharm Biomed Anal 85:245–252.
   PubMed Web of Science ®Google Scholar
• Xu H, Kulkarni KH, Singh R, et al. (2009). Disposition of naringenin via glucuronidation pathway is affected by compensating efflux transporters of hydrophilic glucuronides. Mol Pharm 6:1703–1715.
   PubMed Web of Science ®Google Scholar
• Yabuuchi H, Tanaka K, Maeda M, et al. (2008). Cloning of the dog bile salt export pump (BSEP; ABCB11) and functional comparison with the human and rat proteins. Biopharm Drug Dispos 29:441–448.
   PubMed Web of Science ®Google Scholar
• Yamamoto T, Ito K, Honma M, et al. (2007). Cholesterol-lowering effect of ezetimibe in uridine diphosphate glucuronosyltransferase 1A-deficient (Gunn) rats. Drug Metab Dispos 35:1455–1458.
   PubMed Web of Science ®Google Scholar
• Yang K, Pfeifer ND, Hardwick RN, et al. (2014). An experimental approach to evaluate the impact of impaired transport function on hepatobiliary drug disposition using Mrp2-deficient TR- rat sandwich-cultured hepatocytes in combination with Bcrp knockdown. Mol Pharm 11:766–775.
   PubMed Web of Science ®Google Scholar
• Yang Z, Zhu W, Gao S, et al. (2012). Breast cancer resistance protein (ABCG2) determines distribution of genistein phase II metabolites: Reevaluation of the roles of ABCG2 in the disposition of genistein. Drug Metab Dispos 40:1883–1893.
   PubMed Web of Science ®Google Scholar
• Yeh SL, Lin YC, Lin YL, et al. (2016). Comparing the metabolism of quercetin in rats, mice and gerbils. Eur J Nutr 55:413–422.
   PubMed Web of Science ®Google Scholar
• Yin H, Bennett G, Jones JP. (1994). Mechanistic studies of uridine diphosphate glucuronosyltransferase. Chem Biol Interact 90:47–58.
   PubMed Web of Science ®Google Scholar
• Younis IR, Malone S, Friedman HS, et al. (2009). Enterohepatic recirculation model of irinotecan (CPT-11) and metabolite pharmacokinetics in patients with glioma. Cancer Chemother Pharmacol 63:517–524.
   PubMed Web of Science ®Google Scholar
• Yue Q, Chen YH, Mulder T, et al. (2011). Absorption, distribution, metabolism, and excretion of [(1)(4)C]GDC-0449 (vismodegib), an orally active hedgehog pathway inhibitor, in rats and dogs: A unique metabolic pathway via pyridine ring opening. Drug Metab Dispos 39:952–965.
   PubMed Web of Science ®Google Scholar
• Yue Q, Mulder T, Rudewicz PJ, et al. (2013). Evaluation of metabolism and disposition of GDC-0152 in rats using 14C labeling strategy at two different positions: A novel formation of hippuric acid from 4-phenyl-5-amino-1,2,3-thiadiazole. Drug Metab Dispos 41:508–517.
   PubMed Web of Science ®Google Scholar
• Zamek-Gliszczynski MJ, Chu X, Polli JW, et al. (2014). Understanding the transport properties of metabolites: Case studies and considerations for drug development. Drug Metab Dispos 42:650–664.
   PubMed Web of Science ®Google Scholar
• Zamek-Gliszczynski MJ, Day JS, Hillgren KM, Phillips DL. (2011). Efflux transport is an important determinant of ethinylestradiol glucuronide and ethinylestradiol sulfate pharmacokinetics. Drug Metab Dispos 39:1794–1800.
   PubMed Web of Science ®Google Scholar
• Zamek-Gliszczynski MJ, Hoffmaster KA, Humphreys JE, et al. (2006a). Differential involvement of Mrp2 (Abcc2) and Bcrp (Abcg2) in biliary excretion of 4-methylumbelliferyl glucuronide and sulfate in the rat. J Pharmacol Exp Ther 319:459–467.
   PubMed Web of Science ®Google Scholar
• Zamek-Gliszczynski MJ, Hoffmaster KA, Nezasa K, Brouwer KL. (2008). Apparent differences in mechanisms of harmol sulfate biliary excretion in mice and rats. Drug Metab Dispos 36:2156–2158.
   PubMed Web of Science ®Google Scholar
• Zamek-Gliszczynski MJ, Hoffmaster KA, Nezasa K, et al. (2006b). Integration of hepatic drug transporters and phase II metabolizing enzymes: Mechanisms of hepatic excretion of sulfate, glucuronide, and glutathione metabolites. Eur J Pharm Sci 27:447–486.
   PubMed Web of Science ®Google Scholar
• Zamek-Gliszczynski MJ, Nezasa K, Tian X, et al. (2006c). The important role of Bcrp (Abcg2) in the biliary excretion of sulfate and glucuronide metabolites of acetaminophen, 4-methylumbelliferone, and harmol in mice. Mol Pharmacol 70:2127–2133.
   PubMed Web of Science ®Google Scholar
• Zelcer N, Saeki T, Reid G, et al. (2001). Characterization of drug transport by the human multidrug resistance protein 3 (ABCC3). J Biol Chem 276:46400–46407.
   PubMed Web of Science ®Google Scholar
• Zelcer N, van de Wetering K, Hillebrand M, et al. (2005). Mice lacking multidrug resistance protein 3 show altered morphine pharmacokinetics and morphine-6-glucuronide antinociception. Proc Natl Acad Sci U S A 102:7274–7279.
   PubMed Web of Science ®Google Scholar
• Zeng M, Sun R, Basu S, et al. (2016). Disposition of flavonoids via recycling: Direct biliary excretion of enterically or extrahepatically derived flavonoid glucuronides. Mol Nutr Food Res 60:1006–1019.
   PubMed Web of Science ®Google Scholar
• Zhang L, Lin G, Kovacs B, et al. (2007). Mechanistic study on the intestinal absorption and disposition of baicalein. Eur J Pharm Sci 31:221–231.
   PubMed Web of Science ®Google Scholar
• Zhang X, Dong D, Wang H, et al. (2015). Stable knock-down of efflux transporters leads to reduced glucuronidation in UGT1A1-overexpressing HeLa cells: The evidence for glucuronidation-transport interplay. Mol Pharm 12:1268–1278.
   PubMed Web of Science ®Google Scholar
• Zhao M, Ding W, Wang S, et al. (2016). Simultaneous determination of nine coumarins in rat plasma by HPLC-MS/MS for pharmacokinetics studies following oral administration of Fraxini Cortex extract. J Chromatogr B Analyt Technol Biomed Life Sci 1025:25–32.
   PubMed Web of Science ®Google Scholar
• Zhao X, Yang DH, Zhou QL, et al. (2013). Identification of metabolites in WZS-miniature pig urine after oral administration of Danshen decoction by HPLC coupled with diode array detection with electrospray ionization tandem ion trap and time-of-flight mass spectrometry. Biomed Chromatogr 27:720–735.
   PubMed Web of Science ®Google Scholar
• Zhong K, Li X, Xie C, et al. (2014). Effects of renal impairment on the pharmacokinetics of morinidazole: Uptake transporter-mediated renal clearance of the conjugated metabolites. Antimicrob Agents Chemother 58:4153–4161.
   PubMed Web of Science ®Google Scholar
• Zhou Q, Zheng Z, Xia B, et al. (2010). Use of isoform-specific UGT metabolism to determine and describe rates and profiles of glucuronidation of wogonin and oroxylin A by human liver and intestinal microsomes. Pharm Res 27:1568–1583.
   PubMed Web of Science ®Google Scholar
• Zhou X, Li L, Deng P, et al. (2013). Characterization of metabolites of GLS4 in humans using ultrahigh-performance liquid chromatography/quadrupole time-of-flight mass spectrometry. Rapid Commun Mass Spectrom 27:2483–2492.
   PubMed Web of Science ®Google Scholar
• Zhu W, Xu H, Wang SW, Hu M. (2010). Breast cancer resistance protein (BCRP) and sulfotransferases contribute significantly to the disposition of genistein in mouse intestine. AAPS J 12:525–536.
   PubMed Web of Science ®Google Scholar
• Zhu Y, Li L, Deng P, et al. (2016). Characterization of TPN729 metabolites in humans using ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry. J Pharm Biomed Anal 117:217–226.
   PubMed Web of Science ®Google Scholar