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Review Article

Clinical determinants of calcineurin inhibitor disposition: a mechanistic review

, &
Pages 88-112 | Received 15 Dec 2015, Accepted 02 Feb 2016, Published online: 25 Feb 2016

References

  • Akagi H, Reynolds A, Hjelm M. (1991). Cyclosporin A and its metabolites, distribution in blood and tissues. J Int Med Res 19:1–18.
  • Akhlaghi F, McLachlan AJ, Keogh AM, Brown KF. (1997). Effect of simvastatin on cyclosporine unbound fraction and apparent blood clearance in heart transplant recipients. Br J Clin Pharmacol 44:537–542.
  • Akhlaghi F, Trull AK. (2002). Distribution of cyclosporin in organ transplant recipients. Clin Pharmacokinet 41:615–637.
  • Alexander JW, Goodman H. (2007). Gastric bypass in chronic renal failure and renal transplant. Nutr Clin Pract 22:16–21.
  • Al-Jenoobi FI, Al-Suwayeh SA, Muzaffar I, et al. (2013). Effects of Nigella sativa and Lepidium sativum on cyclosporine pharmacokinetics. BioMed Res Int 2013:953520
  • Aller SG, Yu J, Ward A, et al. (2009). Structure of P-glycoprotein reveals a molecular basis for poly-specific drug binding. Science 323:1718–1722.
  • Amundsen R, Åsberg A, Ohm IK, Christensen H. (2012). Cyclosporine A- and tacrolimus-mediated inhibition of CYP3A4 and CYP3A5 in vitro. Drug Metab Dispos 40:655–661.
  • Anderson GD, Lynn AM. (2009). Optimizing pediatric dosing: A developmental pharmacologic approach. Pharmacotherapy 29:680–690.
  • Anlamlert W, Sermsappasuk P, Yokubol D, Jones S. (2015). Pomelo enhances cyclosporine bioavailability in healthy male Thai volunteers. J Clin Pharmacol 55:377–383.
  • Anonymous. International HapMap Project. Available from: http://hapmap.ncbi.nlm.nih.gov [last accessed 15 June 2015].
  • Anuchapreeda S, Leechanachai P, Smith MM, et al. (2002). Modulation of P-glycoprotein expression and function by curcumin in multidrug-resistant human KB cells. Biochem Pharmacol 64:573–582.
  • Asberg A, Midtvedt K, van Guilder M, et al. (2013). Inclusion of CYP3A5 genotyping in a nonparametric population model improves dosing of tacrolimus early after transplantation. Transpl Int 26:1198–1207.
  • Astellas Pharma US. (2013). Tacrolimus (Prograf®): Prescribing information. Available from: https://www.astellas.us/docs/prograf.pdf [last accessed 1 Nov 2015].
  • Awni WM, Heim-Duthoy K, Kasiske BL. (1990). Impact of lipoproteins on cyclosporine pharmacokinetics and biological activity in transplant patients. Transplant Proc 22:1193–1196.
  • Bailey DG, Dresser GK, Leake BF, Kim RB. (2007). Naringin is a major and selective clinical inhibitor of organic anion-transporting polypeptide 1A2 (OATP1A2) in grapefruit juice. Clin Pharmacol Ther 81:495–502.
  • Basic S, Hajnsek S, Bozina N, et al. (2008). The influence of C3435T polymorphism of ABCB1 gene on penetration of phenobarbital across the blood-brain barrier in patients with generalized epilepsy. Seizure 17:524–530.
  • Bauer S, Stormer E, Johne A, et al. (2003). Alterations in cyclosporin A pharmacokinetics and metabolism during treatment with St John's wort in renal transplant patients. Br J Clin Pharmacol 55:203–211.
  • Bekersky I, Dressler D, Alak A, et al. (2001a). Comparative tacrolimus pharmacokinetics: Normal versus mildly hepatically impaired subjects. J Clin Pharmacol 41:628–635.
  • Bekersky I, Dressler D, Mekki Q. (2001b). Effect of time of meal consumption on bioavailability of a single oral 5 mg tacrolimus dose. J Clin Pharmacol 41:289–297.
  • Bekersky I, Dressler D, Mekki QA. (2001c). Effect of low- and high-fat meals on tacrolimus absorption following 5 mg single oral doses to healthy human subjects. J Clin Pharmacol 41:176–182.
  • Berggren S, Gall C, Wollnitz N, et al. (2007). Gene and protein expression of P-glycoprotein, MRP1, MRP2, and CYP3A4 in the small and large human intestine. Mol Pharm 4:252–257.
  • Bergmann TK, Hennig S, Barraclough KA, et al. (2014). Population pharmacokinetics of tacrolimus in adult kidney transplant patients: Impact of CYP3A5 genotype on starting dose. Ther Drug Monitor 36:62–70.
  • Beysens AJ, Wijnen RM, Beuman GH, et al. (1991). FK 506: Monitoring in plasma or in whole blood? Transplant Proc 23:2745–2747.
  • Bhardwaj RK, Glaeser H, Becquemont L, et al. (2002). Piperine, a major constituent of black pepper, inhibits human P-glycoprotein and CYP3A4. J Pharmacol Exp Ther 302:645–650.
  • Bistrup C, Nielsen FT, Jeppesen UE, Dieperink H. (2001). Effect of grapefruit juice on Sandimmun Neoral absorption among stable renal allograft recipients. Nephrol Dial Transplant 16:373–377.
  • Blokzijl H, Vander Borght S, Bok LIH, et al. (2007). Decreased P-glycoprotein (P-gp/MDR1) expression in inflamed human intestinal epithelium is independent of PXR protein levels. Inflamm Bowel Dis 13:710–720.
  • Böttiger Y, Undre NA, Säwe J, et al. (2002). Effect of bile flow on the absorption of tacrolimus in liver allograft transplantation. Transplant Proc 34:1544–1545.
  • Bourget P, Fernandez H, Bismuth H, Papiernik E. (1990). Transplacental passage of cyclosporine after liver transplantation. Transplantation 49:663.
  • Budzinski JW, Foster BC, Vandenhoek S, Arnason JT. (2000). An in vitro evaluation of human cytochrome P450 3A4 inhibition by selected commercial herbal extracts and tinctures. Phytomedicine 7:273–282.
  • Burger CI, Clase CM, Gangji AS. (2010). Case report: Drug interaction between tacrolimus and amiodarone with QT prolongation. Transplantation 89:1166–1167.
  • Butterweck V, Derendorf H, Gaus W, et al. (2004). Pharmacokinetic herb-drug interactions: Are preventive screenings necessary and appropriate? Planta Med 70:784–791.
  • Campana C, Regazzi MB, Buggia I, Molinaro M. (1996). Clinically significant drug interactions with cyclosporin. An update. Clin Pharmacokinet 30:141–179.
  • Canafax DM, Graves NM, Hilligoss DM, et al. (1991). Interaction between cyclosporine and fluconazole in renal allograft recipients. Transplantation 51:1014–1018.
  • Canaparo R, Finnstrom N, Serpe L, et al. (2007). Expression of CYP3A isoforms and P-glycoprotein in human stomach, jejunum and ileum. Clin Exp Pharmacol Physiol 34:1138–1144.
  • Capron A, Mourad M, De Meyer M, et al. (2010). CYP3A5 and ABCB1 polymorphisms influence tacrolimus concentrations in peripheral blood mononuclear cells after renal transplantation. Pharmacogenomics 11:703–714.
  • Chen D, Guo F, Shi J, et al. (2013). Association of hemoglobin levels, CYP3A5, and NR1I3 gene polymorphisms with tacrolimus pharmacokinetics in liver transplant patients. Drug Metab Pharmacokinet 29:1–26.
  • Chen M, Ma L, Drusano GL, et al. (2006). Sex differences in CYP3A activity using intravenous and oral midazolam. Clin Pharmacol Ther 80:531–538.
  • Chiang H-M, Chao P-DL, Hsiu S-L, et al. (2006). Ginger significantly decreased the oral bioavailability of cyclosporine in rats. Am J Chin Med 34:845–855.
  • Chow FS, Piekoszewski W, Jusko WJ. (1997). Effect of hematocrit and albumin concentration on hepatic clearance of tacrolimus (FK506) during rabbit liver perfusion. Drug Metab Dispos 25:610–616.
  • Christiaans M, Van Duijnhoven E, Beysens T, et al. (1998). Effect of breakfast on the oral bioavailability of tacrolimus and changes in pharmacokinetics at different times posttransplant in renal transplant recipients. Transplant Proc 30:1271–1273.
  • Christians U, Jacobsen W, Benet LZ, Lampen A. (2002). Mechanisms of clinically relevant drug interactions associated with tacrolimus. Clin Pharmacokinet 41:813–851.
  • Copeland KR, Thliveris JA, Yatscoff RW. (1990). Toxicity of cyclosporine metabolites. Ther Drug Monitor 12:525–532.
  • Coscia LA, Constantinescu S, Moritz MJ, et al. (2010). Report from the National Transplantation Pregnancy Registry (NTPR): Outcomes of pregnancy after transplantation. Clin Transpl 2010:65–85.
  • Cotreau MM, von Moltke LL, Greenblatt DJ. (2005). The influence of age and sex on the clearance of cytochrome P450 3A substrates. Clin Pharmacokinet 44:33–60.
  • Crettol S, Venetz J-P, Fontana M, et al. (2008). Influence of ABCB1 genetic polymorphisms on cyclosporine intracellular concentration in transplant recipients. Pharmacogenet Genomics 18:307–315.
  • Curtis JJ, Jones P, Barbeito R. (2006). Large within-day variation in cyclosporine absorption: Circadian variation or food effect? Clin J Am Soc Nephrol 1:462–466.
  • De Denus S, Zakrzewski M, Barhdadi A, et al. (2011). Association between renal function and CYP3A5 genotype in heart transplant recipients treated with calcineurin inhibitors. J Heart Lung Transplant 30:326–331.
  • de Jonge H, Kuypers DR, Verbeke K, Vanrenterghem Y. (2010). Reduced C0 concentrations and increased dose requirements in renal allograft recipients converted to the novel once-daily tacrolimus formulation. Transplantation 90:523–529.
  • de Jonge H, de Loor H, Verbeke K, et al. (2012). In vivo CYP3A4 activity, CYP3A5 genotype, and hematocrit predict tacrolimus dose requirements and clearance in renal transplant patients. Clin Pharmacol Ther 92:366–375.
  • de Jonge H, de Loor H, Verbeke K, et al. (2013). Impact of CYP3A5 genotype on tacrolimus versus midazolam clearance in renal transplant recipients: New insights in CYP3A5-mediated drug metabolism. Pharmacogenomics 14:1467–1480.
  • de Jonge H, de Loor H, Verbeke K, et al. (2011). In vivo CYP3A activity is significantly lower in cyclosporine-treated as compared with tacrolimus-treated renal allograft recipients. Clin Pharmacol Ther 90:414–422.
  • de Jonge H, Vanhove T, de Loor H, et al. (2015). Progressive decline in tacrolimus clearance after renal transplantation is partially explained by decreasing CYP3A4 activity and increasing hematocrit. Br J Clin Pharmacol 80:548–559.
  • Dey S, Ramachandra M, Pastan I, et al. (1997). Evidence for two nonidentical drug-interaction sites in the human P-glycoprotein. Proc Natl Acad Sci USA 94:10594–10599.
  • Dresser GK, Bailey DG, Leake BF, et al. (2002). Fruit juices inhibit organic anion transporting polypeptide-mediated drug uptake to decrease the oral availability of fexofenadine. Clin Pharmacol Ther 71:11–20.
  • Ducharme MP, Warbasse LH, Edwards DJ. (1995). Disposition of intravenous and oral cyclosporine after administration with grapefruit juice. Clin Pharmacol Ther 57:485–491.
  • Dürr D, Stieger B, Kullak-Ublick GA, et al. (2000). St John's Wort induces intestinal P-glycoprotein/MDR1 and intestinal and hepatic CYP3A4. Clin Pharmacol Ther 68:598–604.
  • Egashira K, Sasaki H, Higuchi S, Ieiri I. (2012). Food-drug interaction of tacrolimus with pomelo, ginger, and turmeric juice in rats. Drug Metab Pharmacokinet 27:242–247.
  • EMA. (2007). Advagraf: EPAR. Available from: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Scientific_Discussion/human/000712/WC500022237.pdf [last accessed 1 Nov 2015].
  • Englund G, Jacobson A, Rorsman F, et al. (2007). Efflux transporters in ulcerative colitis: Decreased expression of BCRP (ABCG2) and Pgp (ABCB1). Inflamm Bowel Dis 13:291–297.
  • Englund G, Lundquist P, Skogastierna C, et al. (2014). Cytochrome p450 inhibitory properties of common efflux transporter inhibitors. Drug Metab Dispos 42:441–447.
  • Estudante M, Morais JG, Soveral G, Benet LZ. (2013). Intestinal drug transporters: An overview. Adv Drug Deliv Rev 65:1340–1356.
  • European Medicines Agency. (2012). Guideline on the Investigation of Drug Interactions Guideline on the Investigation of Drug Interactions Table of contents. Available from: http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2012/07/WC500129606.pdf [last accessed 1 Nov 2015].
  • Evans WE, Relling MV, de Graaf S, et al. (1989). Hepatic drug clearance in children: Studies with indocyanine green as a model substrate. J Pharm Sci 78:452–456.
  • Fakhoury M, Lecordier J, Medard Y, et al. (2006). Impact of inflammation on the duodenal mRNA expression of CYP3A and P-glycoprotein in children with Crohn's disease. Inflamm Bowel Dis 12:745–749.
  • Falck P, Asberg A, Byberg K-T, et al. (2008). Reduced elimination of cyclosporine A in elderly (>65 years) kidney transplant recipients. Transplantation 86:1379–1383.
  • Falck P, Midtvedt K, Van Le TT, et al. (2009). A population pharmacokinetic model of ciclosporin applicable for assisting dose management of kidney transplant recipients. Clin Pharmacokinet 48:615–623.
  • Fanta S, Jonsson S, Backman JT, et al. (2007). Developmental pharmacokinetics of ciclosporin - A population pharmacokinetic study in paediatric renal transplant candidates. Br J Clin Pharmacol 64:772–784.
  • Farrell RJ, Menconi MJ, Keates AC, Kelly CP. (2002). P-glycoprotein-170 inhibition significantly reduces cortisol and ciclosporin efflux from human intestinal epithelial cells and T lymphocytes. Aliment Pharmacol Ther 16:1021–1031.
  • Farrell RJ, Murphy A, Long A, et al. (2000). High multidrug resistance (P-glycoprotein 170) expression in inflammatory bowel disease patients who fail medical therapy. Gastroenterology 118:279–288.
  • FDA. (2012). Guidance for industry. Drug interaction studies study design, data analysis, implications for dosing, and labeling recommendations. Available from: http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm292362.pdf [last accessed 5 Nov 2015].
  • Felipe CR, Silva HT, Machado PGP, et al. (2002). The impact of ethnic miscegenation on tacrolimus clinical pharmacokinetics and therapeutic drug monitoring. Clin Transplant 16:262–272.
  • Ferraresso M, Tirelli A, Ghio L, et al. (2007). Influence of the CYP3A5 genotype on tacrolimus pharmacokinetics and pharmacodynamics in young kidney transplant recipients. Pediatr Transplant 11:296–300.
  • Ferrari SL, Goffin E, Mourad M, et al. (1994). The interaction between clarithromycin and cyclosporine in kidney transplant recipients. Transplantation 58:725–727.
  • Ferreira RJ, Ferreira MJU, Dos Santos DJVa. (2013). Molecular docking characterizes substrate-binding sites and efflux modulation mechanisms within P-glycoprotein. J Chem Inf Model 53:1747–1760.
  • First MR, Schroeder TJ, Monaco AP, et al. (1996). Cyclosporine bioavailability: Dosing implications and impact on clinical outcomes in select transplantation subpopulations. Clin Transpl 10:55–59.
  • Fitzsimmons WE, Bekersky I, Dressler D, et al. (1998). Demographic considerations in tacrolimus pharmacokinetics. Transplant Proc 30:1359–1364.
  • Floren LC, Bekersky I, Benet LZ, et al. (1997). Tacrolimus oral bioavailability doubles with coadministration of ketoconazole. Clin Pharmacol Ther 62:41–49.
  • Fojo AT, Ueda K, Slamon DJ, et al. (1987). Expression of a multidrug-resistance gene in human tumors and tissues. Proc Natl Acad Sci USA 84:265–269.
  • Fricker G, Miller DS. (2004). Modulation of drug transporters at the blood-brain barrier. Pharmacology 70:169–176.
  • Fromm MF, Kauffmann HM, Fritz P, et al. (2000). The effect of rifampin treatment on intestinal expression of human MRP transporters. Am J Pathol 157:1575–1580.
  • Fruhwirth M, Fischer H, Simma B, et al. (2001). Rotavirus infection as cause of tacrolimus elevation in solid-organ-transplanted children. Pediatr Transplant 5:88–92.
  • Fukatsu S, Yano I, Igarashi T, et al. (2001). Population pharmacokinetics of tacrolimus in adult recipients receiving living-donor liver transplantation. Eur J Clin Pharmacol 57:479–484.
  • Fukudo M, Yano I, Masuda S, et al. (2006). Population pharmacokinetic and pharmacogenomic analysis of tacrolimus in pediatric living-donor liver transplant recipients. Clin Pharmacol Ther 80:331–345.
  • Fulop TJ, Worum I, Csongor J, et al. (1985). Body composition in elderly people. I. Determination of body composition by multiisotope method and the elimination kinetics of these isotopes in healthy elderly subjects. Gerontology 31:6–14.
  • Ganapathy V, Prasad PD, Ganapathy ME, Leibach FH. (2000). Placental transporters relevant to drug distribution across the maternal-fetal interface. J Pharmacol Exp Ther 294:413–420.
  • Gandhi AS, Guo T, Shah P, et al. (2012). CYP3A-dependent drug metabolism is reduced in bacterial inflammation in mice. Br J Pharmacol 166:2176–2187.
  • Garcia Sanchez MJ, Manzanares C, Santos-Buelga D, et al. (2001). Covariate effects on the apparent clearance of tacrolimus in paediatric liver transplant patients undergoing conversion therapy. Clin Pharmacokinet 40:63–71.
  • Garg V, van Heeswijk R, Lee JE, et al. (2011). Effect of telaprevir on the pharmacokinetics of cyclosporine and tacrolimus. Hepatology (Baltimore, MD) 54:20–27.
  • Geick A, Eichelbaum M, Burk O. (2001). Nuclear receptor response elements mediate induction of intestinal MDR1 by rifampin. J Biol Chem 276:14581–14587.
  • Gertz M, Cartwright CM, Hobbs MJ, et al. (2013). Cyclosporine inhibition of hepatic and intestinal CYP3A4, uptake and efflux transporters: Application of PBPK Modeling in the assessment of drug-drug interaction potential. Pharmaceutical Research 30:761–780.
  • Gervasini G, Garcia M, Macias RM, et al. (2012). Impact of genetic polymorphisms on tacrolimus pharmacokinetics and the clinical outcome of renal transplantation. Transpl Int 25:471–480.
  • Gervot L, Carriere V, Costet P, et al. (1996). CYP3A5 is the major cytochrome P450 3A expressed in human colon and colonic cell lines. Environ Toxicol Pharmacol 2:381–388.
  • Gibbs MA, Thummel KE, Shen DD, Kunze KL. (1999). Inhibition of cytochrome P-450 3A (CYP3A) in human intestinal and liver microsomes: Comparison of Ki values and impact of CYP3A5 expression. Drug Metab Dispos 27:180–187.
  • Glaeser H, Drescher S, Eichelbaum M, Fromm MF. (2005). Influence of rifampicin on the expression and function of human intestinal cytochrome P450 enzymes. Br J Clin Pharmacol 59:199–206.
  • Glowacki F, Lionet A, Buob D, et al. (2011a). CYP3A5 and ABCB1 polymorphisms in donor and recipient: Impact on Tacrolimus dose requirements and clinical outcome after renal transplantation. Nephrol Dial Transplant 26:3046–3050.
  • Glowacki F, Lionet A, Hammelin J-P, et al. (2011b). Influence of cytochrome P450 3A5 (CYP3A5) genetic polymorphism on the pharmacokinetics of the prolonged-release, once-daily formulation of tacrolimus in stable renal transplant recipients. Clin Pharmacokinet 50:451–459.
  • Golubović B, Vučićević K, Radivojević D, et al. (2014). Total plasma protein effect on tacrolimus elimination in kidney transplant patients-population pharmacokinetic approach. Eur J Pharm Sci52:34–40.
  • Gomez DY, Wacher VJ, Tomlanovich SJ, et al. (1995). The effects of ketoconazole on the intestinal metabolism and bioavailability of cyclosporine. Clin Pharmacol Ther 58:15–19.
  • Gorski JC, Vannaprasaht S, Hamman MA, et al. (2003). The effect of age, sex, and rifampin administration on intestinal and hepatic cytochrome P450 3A activity. Clin Pharmacol Ther 74:275–287.
  • Grenier J, Fradette C, Morelli G, et al. (2006). Pomelo juice, but not cranberry juice, affects the pharmacokinetics of cyclosporine in humans. Clin Pharmacol Ther 79:255–262.
  • Grevel J. (1986). Absorption of cyclosporine A after oral dosing. Transplant Proc 18:9–15.
  • Grevel J, Nüesch E, Abisch E, Kutz K. (1986). Pharmacokinetics of oral cyclosporin A (Sandimmun) in healthy subjects. Eur J Clin Pharmacol 31:211–216.
  • Grover A, Frassetto LA, Benet LZ, Chakkera HA. (2011). Pharmacokinetic differences corroborate observed low tacrolimus dosage in Native American renal transplant patients. Drug Metab Dispos 39:2017–2019.
  • Gupta SK, Bakran A, Johnson RW, Rowland M. (1989). Cyclosporin-erythromycin interaction in renal transplant patients. Br J Clin Pharmacol 27:475–481.
  • Hamman MA, Bruce MA, Haehner-Daniels BD, Hall SD. (2001). The effect of rifampin administration on the disposition of fexofenadine. Clin Pharmacol Ther 69:114–121.
  • Hebert MF, Fisher RM, Marsh CL, et al. (1999). Effects of rifampin on tacrolimus pharmacokinetics in healthy volunteers. J Clin Pharmacol 39:91–96.
  • Hebert MF, Park JM, Chen Y-L, et al. (2004). Effects of St. John's wort (Hypericum perforatum) on tacrolimus pharmacokinetics in healthy volunteers. J Clin Pharmacol 44:89–94.
  • Hebert MF, Roberts JP, Prueksaritanont T, Benet LZ. (1992). Bioavailability of cyclosporine with concomitant rifampin administration is markedly less than predicted by hepatic enzyme induction. Clin Pharmacol Ther 52:453–457.
  • Hesselink Da, Bouamar R, Elens L, et al. (2014). The role of pharmacogenetics in the disposition of and response to tacrolimus in solid organ transplantation. Clin Pharmacokinet 53:123–139.
  • Hesselink DA, van Schaik RHN, van Agteren M, et al. (2008). CYP3A5 genotype is not associated with a higher risk of acute rejection in tacrolimus-treated renal transplant recipients. Pharmacogenet Genomics 18:339–348.
  • Hesselink DA, van Schaik RH, van der Heiden IP, et al. (2003). Genetic polymorphisms of the CYP3A4, CYP3A5, and MDR-1 genes and pharmacokinetics of the calcineurin inhibitors cyclosporine and tacrolimus. Clin Pharmacol Ther 74:245–254.
  • Hochleitner BW, Bosmuller C, Nehoda H, et al. (2001). Increased tacrolimus levels during diarrhea. Transpl Int 14:230–233.
  • Honcharik N. (1991). The effect of food on cyclosporine absorption. Clin Biochem 24:89–92.
  • Hou Y-C, Lin S-P, Chao P-DL. (2012). Liquorice reduced cyclosporine bioavailability by activating P-glycoprotein and CYP 3A. Food Chem 135:2307–2312.
  • Hsiu S-L, Hou Y-C, Wang Y-H, et al. (2002). Quercetin significantly decreased cyclosporin oral bioavailability in pigs and rats. Life Sci 72:227–235.
  • Hulskotte E, Gupta S, Xuan F, et al. (2012). Pharmacokinetic interaction between the hepatitis C virus protease inhibitor boceprevir and cyclosporine and tacrolimus in healthy volunteers. Hepatology (Baltimore, MD) 56:1622–1630.
  • Hunt CM, Westerkam WR, Stave GM, Wilson JA. (1992). Hepatic cytochrome P-4503A (CYP3A) activity in the elderly. Mech Ageing Dev 64:189–199.
  • Hurst AL, Clark N, Carpenter TC, et al. (2015). Supra-therapeutic tacrolimus concentrations associated with concomitant nicardipine in pediatric liver transplant recipients. Pediatr Transplant 19:E83–E87.
  • Jacobson P, Ng J, Ratanatharathorn V, et al. (2001). Factors affecting the pharmacokinetics of tacrolimus (FK506) in hematopoietic cell transplant (HCT) patients. Bone Marrow Transplant 28:753–758.
  • Jacobson P, Schladt D, Israni A, et al. (2012a). Genetic and clinical determinants of early, acute calcineurin inhibitor-related nephrotoxicity: Results from a kidney transplant consortium. Transplantation 93:624–631.
  • Jacobson P, Schladt D, Oetting WS, et al. (2012b). Lower calcineurin inhibitor doses in older compared to younger kidney transplant recipients yield similar troughs. Am J Transplant 12:3326–3336.
  • Jain AB, Fung JJ, Tzakis AG, et al. (1991). Comparative study of cyclosporine and FK 506 dosage requirements in adult and pediatric orthotopic liver transplant patients. Transplant Proc 23:2763–2766.
  • Jain AB, Venkataramanan R, Cadoff E, et al. (1990). Effect of hepatic dysfunction and T tube clamping on FK 506 pharmacokinetics and trough concentrations. Transplant Proc 22:57–59.
  • Jain AKB, Venkataramanan R, Shapiro R, et al. (2002). The interaction between antiretroviral agents and tacrolimus in liver and kidney transplant patients. Liver Transplant 8:841–845.
  • Jantz AS, Patel SJ, Suki WN, et al. (2013). Treatment of acute tacrolimus toxicity with phenytoin in solid organ transplant recipients. Case Rep Transplant 2013:375263.
  • Jusko WJ, Piekoszewski W, Klintmalm GB, et al. (1995). Pharmacokinetics of tacrolimus in liver transplant patients. Clin Pharmacol Ther 57:281–290.
  • Kahan BD, Kramer WG, Wideman CA, et al. (1986). Analysis of pharmacokinetic profiles in 232 renal and 87 cardiac allograft recipients treated with cyclosporine. Transplant Proc 18:115–119.
  • Kalitsky-Szirtes J, Shayeganpour A, Brocks DR, Piquette-Miller M. (2004). Suppression of drug-metabolizing enzymes and efflux transporters in the intestine of endotoxin-treated rats. Drug Metab Dispos 32:20–27.
  • Kanamori M, Takahashi H, Echizen H. (2002). Developmental changes in the liver weight- and body weight-normalized clearance of theophylline, phenytoin and cyclosporine in children. Int J Clin Pharmacol Ther 40:485–492.
  • Kawaguchi-Suzuki M, Frye RF, Zhu H-J, et al. (2014). The effects of milk thistle (Silybum marianum) on human cytochrome P450 activity. Drug Metab Dispos 42:1611–1616.
  • Kelley M, Jain A, Kashyap R, et al. (2005). Change in oral absorption of tacrolimus in a liver transplant recipient after reversal of jejunoileal bypass: Case report. Transplant Proc 37:3165–3167.
  • Kharasch ED, Walker a, Isoherranen N, et al. (2007). Influence of CYP3A5 genotype on the pharmacokinetics and pharmacodynamics of the cytochrome P4503A probes alfentanil and midazolam. Clin Pharmacol Ther 82:410–426.
  • Kim C-S, Choi S-J, Park C-Y, et al. (2010). Effects of silybinin on the pharmacokinetics of tamoxifen and its active metabolite, 4-hydroxytamoxifen in rats. Anticancer Res 30:79–85.
  • Kim I-W, Moon YJ, Ji E, et al. (2012). Clinical and genetic factors affecting tacrolimus trough levels and drug-related outcomes in Korean kidney transplant recipients. Eur J Clin Pharmacol 68:657–669.
  • Kimikawa M, Kamoya K, Toma H, Teraoka S. (2001). Effective oral administration of tacrolimus in renal transplant recipients. Clin Transplant 15:324–329.
  • Knops N, van den Heuvel LP, Masereeuw R, et al. (2015). The functional implications of common genetic variation in CYP3A5 and ABCB1 in human proximal tubule cells. Mol Pharm 12:758–768.
  • Koch I, Weil R, Wolbold R, et al. (2002). Interindividual variability and tissue-specificity in the expression of cytochrome P450 3A mRNA. Drug Metab Dispos 30:1108–1114.
  • Kolars JC, Awni WM, Merion RM, Watkins PB. (1991). First-pass metabolism of cyclosporin by the gut. Lancet 338:1488–1490.
  • Kolars JC, Lown KS, Schmiedlin-Ren P, et al. (1994). CYP3A gene expression in human gut epithelium. Pharmacogenetics 4:247–259.
  • Kovarik JM, Koelle EU. (1999). Cyclosporin pharmacokinetics in the elderly. Drugs Aging 15:197–205.
  • Kramer MR, Amital A, Fuks L, Shitrit D. (2011). Voriconazole and itraconazole in lung transplant recipients receiving tacrolimus (FK 506): Efficacy and drug interaction. Clin Transplant 25:163–167.
  • Kumana CR, Tong MKL, Li C-S, et al. (2003). Diltiazem co-treatment in renal transplant patients receiving microemulsion cyclosporin. Br J Clin Pharmacol 56:670–678.
  • Kunicki PK, Sobieszczanska-Malek M. (2005). Pharmacokinetic interaction between tacrolimus and clarithromycin in a heart transplant patient. Ther Drug Monitor 27:107–108.
  • Kusunoki Y, Ikarashi N, Hayakawa Y, et al. (2014). Hepatic early inflammation induces downregulation of hepatic cytochrome P450 expression and metabolic activity in the dextran sulfate sodium-induced murine colitis. Eur J Pharm Sci 54:17–27.
  • Kuypers DR, de Jonge H, Naesens M, Vanrenterghem Y. (2008). Effects of CYP3A5 and MDR1 single nucleotide polymorphisms on drug interactions between tacrolimus and fluconazole in renal allograft recipients. Pharmacogenet Genomics 18:861–868.
  • Kuypers DRJ, Claes K, Evenepoel P, et al. (2004a). Time-related clinical determinants of long-term tacrolimus pharmacokinetics in combination therapy with mycophenolic acid and corticosteroids: A prospective study in one hundred de novo renal transplant recipients. Clin Pharmacokinet 43:741–762.
  • Kuypers DRJ, Claes K, Evenepoel P, et al. (2004b). The rate of gastric emptying determines the timing but not the extent of oral tacrolimus absorption: Simultaneous measurement of drug exposure and gastric emptying by carbon-14-octanoic acid breath test in stable renal allograft recipients. Drug Metab Dispos 32:1421–1425.
  • Kuypers DRJ, de Jonge H, Naesens M, et al. (2007). CYP3A5 and CYP3A4 but not MDR1 single-nucleotide polymorphisms determine long-term tacrolimus disposition and drug-related nephrotoxicity in renal recipients. Clin Pharmacol Ther 82:711–725.
  • Kuypers DRJ, de Jonge H, Naesens M, Vanrenterghem Y. (2010a). A prospective, open-label, observational clinical cohort study of the association between delayed renal allograft function, tacrolimus exposure, and CYP3A5 genotype in adult recipients. Clin Ther 32:2012–2023.
  • Kuypers DRJ, Naesens M, Jonge HD. (2010b). Tacrolimus dose requirements and CYP3A5 genotype and the development of calcineurin inhibitor-associated nephrotoxicity in renal allograft recipients. Ther Drug Monit 32:394–404.
  • Lai M-Y, Hsiu S-L, Hou Y-C, et al. (2004). Significant decrease of cyclosporine bioavailability in rats caused by a decoction of the roots of Scutellaria baicalensis. Planta Med 70:132–137.
  • Langmann T, Moehle C, Mauerer R, et al. (2004). Loss of detoxification in inflammatory bowel disease: Dysregulation of pregnane X receptor target genes. Gastroenterology 127:26–40.
  • Latorre A, Morales E, Gonzalez E, et al. (2002). Clinical management of renal transplant patients with hepatitis C virus infection treated with cyclosporine or tacrolimus. Transplant Proc 34:63–64.
  • Lee C-K, Choi J-S. (2010). Effects of silibinin, inhibitor of CYP3A4 and P-glycoprotein in vitro, on the pharmacokinetics of paclitaxel after oral and intravenous administration in rats. Pharmacology 85:350–356.
  • Lee C-M, Pohl J, Morgan ET. (2009). Dual mechanisms of CYP3A protein regulation by proinflammatory cytokine stimulation in primary hepatocyte cultures. Drug Metab Dispos 37:865–872.
  • Lee JR, Muthukumar T, Dadhania D, et al. (2015). Gut microbiota and tacrolimus dosing in kidney transplantation. PLoS One 10:e0122399.
  • Lee JY, Hahn HJ, Son IJ, et al. (2006). Factors affecting the apparent clearance of tacrolimus in Korean adult liver transplant recipients. Pharmacotherapy 26:1069–1077.
  • Legg B, Rowland M. (1987). Cyclosporin: Measurement of fraction unbound in plasma. J Pharm Pharmacol 39:599–603.
  • Lemahieu W, Maes B, Verbeke K, et al. (2005). Cytochrome P450 3A4 and P-glycoprotein activity and assimilation of tacrolimus in transplant patients with persistent diarrhea. Am J Transplant 5:1383–1391.
  • Lemahieu WPD, Maes BD, Ghoos Y, et al. (2003). Measurement of hepatic and intestinal CYP3A4 and PGP activity by combined po + iv [14C]erythromycin breath and urine test. Am J Physiol Gastrointest Liver Physiol 285:G470–G482.
  • Lemahieu WPD, Maes BD, Vanrenterghem Y. (2005). Different evolution of trough and dose levels during the first year after transplantation for tacrolimus versus cyclosporine. Transplant Proc 37:2051–2053.
  • Lemahieu WPD, Maes BD, Verbeke K, Vanrenterghem Y. (2004). CYP3A4 and P-glycoprotein activity in healthy controls and transplant patients on cyclosporin vs. tacrolimus vs. sirolimus. Am J Transplant 4:1514–1522.
  • Li D, Lu W, Zhu J-Y, et al. (2007). Population pharmacokinetics of tacrolimus and CYP3A5, MDR1 and IL-10 polymorphisms in adult liver transplant patients. J Clin Pharm Ther 32:505–515.
  • Li H, Jia W. (2013). Cometabolism of microbes and host: Implications for drug metabolism and drug-induced toxicity. Clin Pharmacol Ther 94:574–581.
  • Li J-L, Wang X-D, Chen S-Y, et al. (2011). Effects of diltiazem on pharmacokinetics of tacrolimus in relation to CYP3A5 genotype status in renal recipients: From retrospective to prospective. Pharmacogenomics J 11:300–306.
  • Lian-Qing G, Fukuda K, Ohta T, Yamazoe Y. (2000). Role of furanocoumarin derivatives on grapefruit juice-mediated inhibition of human CYP3A activity. Drug Metab Dispos 28:766–771.
  • Lill J, Bauer LA, Horn JR, Hansten PD. (2000). Cyclosporine-drug interactions and the influence of patient age. Am J Health Syst Pharm 57:1579–1584.
  • Lin S-P, Chao P-DL, Tsai S-Y, et al. (2011). Citrus grandis peel increases the bioavailability of cyclosporine and tacrolimus, two important immunosuppressants, in rats. J Med Food 14:1463–1468.
  • Lin YS, Dowling ALS, Quigley SD, et al. (2002). Co-regulation of CYP3A4 and CYP3A5 and contribution to hepatic and intestinal midazolam metabolism. Mol Pharmacol 62:162–172.
  • Lindholm A, Henricsson S, Dahlqvist R. (1990). The effect of food and bile acid administration on the relative bioavailability of cyclosporin. Br J Clin Pharmacol 29:541–548.
  • Lindholm A, Welsh M, Alton C, Kahan BD. (1992). Demographic factors influencing cyclosporine pharmacokinetic parameters in patients with uremia: Racial differences in bioavailability. Clin Pharmacol Ther 52:359–371.
  • Liston HL, Markowitz JS, Hunt N, et al. (2001). Lack of citalopram effect on the pharmacokinetics of cyclosporine. Psychosomatics 42:370–372.
  • Litman T, Zeuthen T, Skovsgaard T, Stein WD. (1997). Competitive, non-competitive and cooperative interactions between substrates of P-glycoprotein as measured by its ATPase activity. Biochim Biophys Acta 1361:169–176.
  • Liu C, Shang Y-F, Zhang X-F, et al. (2009). Co-administration of grapefruit juice increases bioavailability of tacrolimus in liver transplant patients: A prospective study. Eur J Clin Pharmacol 65:881–885.
  • Liu F, Li Y, Lan X, et al. (2009). Tacrolimus dosage requirements in living donor liver transplant recipients with small-for-size grafts. World J Gastroenterol 15:3931–3936.
  • Lown KS, Bailey DG, Fontana RJ, et al. (1997). Grapefruit juice increases felodipine oral availability in humans by decreasing intestinal CYP3A protein expression. J Clin Invest 99:2545–2553.
  • Lundahl J, Regardh CG, Edgar B, Johnsson G. (1995). Relationship between time of intake of grapefruit juice and its effect on pharmacokinetics and pharmacodynamics of felodipine in healthy subjects. Eur J Clin Pharmacol 49:61–67.
  • Ma JD, Tsunoda SM, Bertino JS, et al. (2010). Evaluation of in vivo P-glycoprotein phenotyping probes: A need for validation. Clin Pharmacokinet 49:223–237.
  • MacFarlane GD, Venkataramanan R, McDiarmid SV, et al. (2001). Therapeutic drug monitoring of tacrolimus in pediatric liver transplant patients. Pediatr Transplant 5:119–124.
  • Maes BD, Lemahieu W, Kuypers D, et al. (2002). Differential effect of diarrhea on FK506 versus cyclosporine A trough levels and resultant prevention of allograft rejection in renal transplant recipients. Am J Transplant 2:989–992.
  • Mai I, Bauer S, Perloff ES, et al. (2004). Hyperforin content determines the magnitude of the St John's wort-cyclosporine drug interaction. Clin Pharmacol Ther 76:330–340.
  • Mai I, Stormer E, Bauer S, et al. (2003). Impact of St John's wort treatment on the pharmacokinetics of tacrolimus and mycophenolic acid in renal transplant patients. Nephrol Dial Transplant 18:819–822.
  • Makhey VD, Guo A, Norris DA, Hu P, et al. (1998). Characterization of the regional intestinal kinetics of drug efflux in rat and human intestine and in Caco-2 Cells. Pharm Res 15:1160–1167.
  • Mamprin F, Mullins P, Graham T, et al. (1992). Amiodarone-cyclosporine interaction in cardiac transplantation. Am Heart J 123:1725–1726.
  • Mancinelli LM, Frassetto L, Floren LC, et al. (2001). The pharmacokinetics and metabolic disposition of tacrolimus: A comparison across ethnic groups. Clin Pharmacol Ther 69:24–31.
  • Manez R, Martin M, Raman D, et al. (1994). Fluconazole therapy in transplant recipients receiving FK506. Transplantation 57:1521–1523.
  • Manzanares C, Moreno M, Castellanos F, et al. (1998). Influence of hepatitis C virus infection on FK 506 blood levels in renal transplant patients. Transplant Proc 30:1264–1265.
  • Marin-Casino M, Perez-Saez MJ, Crespo M, Echeverria D, Mir M, Pascual J. (2014). Significant tacrolimus and dronedarone interaction in a kidney transplant recipient. Transplantation 98:e33–e34.
  • Markowitz JS, Donovan JL, DeVane CL, et al. (2003). Effect of St John's wort on drug metabolism by induction of cytochrome P450 3A4 enzyme JAMA 290:1500–1504.
  • Markowitz JS, Gill HS, Hunt NM, et al. (1998). Lack of antidepressant-cyclosporine pharmacokinetic interactions. J Clin Psychopharmacol 18:91–93.
  • Marterre WF, Hariharan S, First MR, Alexander JW. (1996). Gastric bypass in morbidly obese kidney transplant recipients. Clin Transplant 10:414–419.
  • Martin C, Berridge G, Higgins CF, et al. (2000). Communication between multiple drug binding sites on P-glycoprotein. Mol Pharmacol 58:624–632.
  • Mathis AS, DiRenzo T, Friedman GS, et al. (2001). Sex and ethnicity may chiefly influence the interaction of fluconazole with calcineurin inhibitors. Transplantation 71:1069–1075.
  • McCune JS, Hawke RL, LeCluyse EL, et al. (2000). In vivo and in vitro induction of human cytochrome P4503A4 by dexamethasone. Clin Pharmacol Ther 68:356–366.
  • McDiarmid SV, Colonna JO II, Shaked A, et al. (1993). Differences in oral FK506 dose requirements between adult and pediatric liver transplant patients. Transplantation 55:1328–1332.
  • Mehta MU, Venkataramanan R, Burckart GJ, et al. (1988). Effect of bile on cyclosporin absorption in liver transplant patients. Br J Clin Pharmacol 25:579–584.
  • Mehta P, Beltz S, Kedar A, et al. (1999). Increased clearance of tacrolimus in children: Need for higher doses and earlier initiation prior to bone marrow transplantation. Bone Marrow Transplant 24:1323–1327.
  • Meier-Kriesche HU, Ojo A, Hanson J, et al. (2000). Increased immunosuppressive vulnerability in elderly renal transplant recipients. Transplantation 69:885–889.
  • Mendonza AE, Zahir H, Gohh RY, Akhlaghi F. (2007). Tacrolimus in diabetic kidney transplant recipients: Pharmacokinetics and application of a limited sampling strategy. Ther Drug Monitor 29:391–398.
  • Mihara A, Mori T, Aisa Y, et al. (2008). Greater impact of oral fluconazole on drug interaction with intravenous calcineurin inhibitors as compared with intravenous fluconazole. Eur J Clin Pharmacol 64:89–91.
  • Miura M, Satoh S, Kagaya H, et al. (2009). No impact of age on dose-adjusted pharmacokinetics of tacrolimus, mycophenolic acid and prednisolone 1 month after renal transplantation. Eur J Clin Pharmacol 65:1047–1053.
  • Möller A, Iwasaki K, Kawamura A, et al. (1999). The disposition of 14C-labeled tacrolimus after intravenous and oral administration in healthy human subjects. Drug Metab Dispos 27:633–636.
  • Moore J, McKnight AJ, Dohler B, et al. (2012). Donor ABCB1 variant associates with increased risk for kidney allograft failure. J Am Soc Nephrol 23:1891–1899.
  • Mouly S, Paine MF. (2003). P-glycoprotein increases from proximal to distal regions of human small intestine. Pharm Res 20:1595–1599.
  • Mueller EA, Kovarik JM, van Bree JB, et al. (1994). Influence of a fat-rich meal on the pharmacokinetics of a new oral formulation of cyclosporine in a crossover comparison with the market formulation. Pharm Res 11:151–155.
  • Naesens M, Lerut E, de Jonge H, et al. (2009). Donor age and renal P-glycoprotein expression associate with chronic histological damage in renal allografts. J Am Soc Nephrol 20:2468–2480.
  • Nagase K, Iwasaki K, Nozaki K, Noda K. (1994). Distribution and protein binding of FK506, a potent immunosuppressive macrolide lactone, in human blood and its uptake by erythrocytes. J Pharm Pharmacol 46:113–117.
  • Naoumov NV, Tredger JM, Steward CM, et al. (1989). Cyclosporin A pharmacokinetics in liver transplant recipients in relation to biliary T-tube clamping and liver dysfunction. Gut 30:391–396.
  • Nara M, Takahashi N, Miura M, et al. (2013). Effect of itraconazole on the concentrations of tacrolimus and cyclosporine in the blood of patients receiving allogeneic hematopoietic stem cell transplants. Eur J Clin Pharmacol 69:1321–1329.
  • Narayanan M, Pankewycz O, El-Ghoroury M, et al. (2013). Outcomes in African American kidney transplant patients receiving tacrolimus and mycophenolic acid immunosuppression. Transplantation 95:566–572.
  • Naud J, Nolin TD, Leblond FA, Pichette V. (2012). Current understanding of drug disposition in kidney disease. J Clin Pharmacol 52:10S–22S.
  • Neylan JF. (1998). Racial differences in renal transplantation after immunosuppression with tacrolimus versus cyclosporine. FK506 Kidney Transplant Study Group. Transplantation 65:515–523.
  • Niioka T, Satoh S, Kagaya H, et al. (2012). Comparison of pharmacokinetics and pharmacogenetics of once- and twice-daily tacrolimus in the early stage after renal transplantation. Transplantation 94:1013–1019.
  • Nishioka T, Ikegami M, Imanishi M, et al. (1990). Interaction between phenobarbital and ciclosporin following renal transplantation: A case report. Hinyokika Kiyo 36:447–450.
  • Niwa T, Yamamoto S, Saito M, et al. (2007). Effect of cyclosporine and tacrolimus on cytochrome p450 activities in human liver microsomes. J Pharm Soc Jpn 127:209–216.
  • Novartis. (2015). Cyclosporine (Neoral®): Prescribing information, Available from: https://www.pharma.us.novartis.com/product/pi/pdf/neoral.pdf [last accessed 1 Nov 2015].
  • Olyaei AJ, deMattos AM, Norman DJ, Bennett WM. (1998). Interaction between tacrolimus and nefazodone in a stable renal transplant recipient. Pharmacotherapy 18:1356–1359.
  • Oo YH, Dudley T, Nightingale P, et al. (2008). Tacrolimus and cyclosporin doses and blood levels in hepatitis C and alcoholic liver disease patients after liver transplantation. Liver Transpl 14:81–87.
  • Op den Buijsch RAM, Christiaans MHL, Stolk LML, et al. (2007). Tacrolimus pharmacokinetics and pharmacogenetics: Influence of adenosine triphosphate-binding cassette B1 (ABCB1) and cytochrome (CYP) 3A polymorphisms. Fundam Clin Pharmacol 21:427–435.
  • Osowski CL, Dix SP, Lin LS, et al. (1996). Evaluation of the drug interaction between intravenous high-dose fluconazole and cyclosporine or tacrolimus in bone marrow transplant patients. Transplantation 61:1268–1272.
  • Paine MF, Khalighi M, Fisher JM, et al. (1997). Characterization of interintestinal and intraintestinal variations in human CYP3A-dependent metabolism. J Pharmacol Exp Ther 283:1552–1562.
  • Paine MF, Shen DD, Kunze KL, et al. (1996). First-pass metabolism of midazolam by the human intestine. Clin Pharmacol Ther 60:14–24.
  • Paine MF, Widmer WW, Hart HL, et al. (2006). A furanocoumarin-free grapefruit juice establishes furanocoumarins as the mediators of the grapefruit juice-felodipine interaction. Am J Clin Nutr 83:1097–1105.
  • Paine MF, Widmer WW, Pusek SN, et al. (2008). Further characterization of a furanocoumarin-free grapefruit juice on drug disposition: Studies with cyclosporine. Am J Clin Nutr 87:863–871.
  • Passey C, Birnbaum AK, Brundage RC, et al. (2011). Dosing equation for tacrolimus using genetic variants and clinical factors. Br J Clin Pharmacol 72:948–957.
  • Pavek P, Fendrich Z, Staud F, et al. (2001). Influence of P-glycoprotein on the transplacental passage of cyclosporine. J Pharm Sci 90:1583–1592.
  • Pawarode A, Shukla S, Minderman H, et al. (2007). Differential effects of the immunosuppressive agents cyclosporin A, tacrolimus and sirolimus on drug transport by multidrug resistance proteins. Cancer Chemother Pharmacol 60:179–188.
  • Pea F, Tavio M, Pavan F, et al. (2008). Drop in trough blood concentrations of tacrolimus after switching from nelfinavir to fosamprenavir in four HIV-infected liver transplant patients. Antivir Ther 13:739–742.
  • Pesavento TE, Jones PA, Julian BA, Curtis JJ. (1996). Amlodipine increases cyclosporine levels in hypertensive renal transplant patients: Results of a prospective study. J Am Soc Nephrol 7:831–835.
  • Piekoszewski W, Chow FS, Jusko WJ. (1993). Disposition of tacrolimus (FK 506) in rabbits. Role of red blood cell binding in hepatic clearance. Drug Metab Dispos 21:690–698.
  • Pou L, Brunet M, Andres I, et al. (1998). Influence of posttransplant time on dose and concentration of tacrolimus in liver transplant patients. Transpl Int 11:S270–S271.
  • Prasad TNV, Subbotina N, Burckart G, et al. (1997). Metabolism of tacrolimus (FK 506) in rat liver microsomes. Effect of rifampin and dexamethasone. Res Commun Mol Pathol Pharmacol 96:107–110.
  • Przepiorka D, Blamble D, Hilsenbeck S, et al. (2000). Tacrolimus clearance is age-dependent within the pediatric population. Bone Marrow Transplant 26:601–605.
  • Qin XL, Chen X, Wang Y, et al. (2014). In vivo to in vitro effects of six bioactive lignans of Wuzhi tablet (Schisandra sphenanthera extract) on the CYP3A/P-glycoprotein-mediated absorption and metabolism of tacrolimus. Drug Metab Dispos 42:193–199.
  • Qiu W, Jiang XH, Liu CX, et al. (2009). Effect of berberine on the pharmacokinetics of substrates of CYP3A and P-gp. Phytother Res 23:1553–1558.
  • Quiros-Tejeira RE, Chang I-F, Bristow LJ, et al. (2005). Treatment of acute tacrolimus whole-blood elevation with phenobarbital in the pediatric liver transplant recipient. Pediatr Transplant 9:792–796.
  • Rae JM, Johnson MD, Lippman ME, Flockhart DA. (2001). Rifampin is a selective, pleiotropic inducer of drug metabolism genes in human hepatocytes: Studies with cDNA and oligonucleotide expression arrays. J Pharmacol Exp Ther 299:849–857.
  • Roberts PJ, Rollins KD, Kashuba ADM, et al. (2008). The influence of CYP3A5 genotype on dexamethasone induction of CYP3A activity in African Americans. Drug Metab Dispos 36:1465–1469.
  • Roberts R, Sketris IS, Abraham I, et al. (1988). Cyclosporine absorption in two patients with short-bowel syndrome. Drug Intell Clin Pharm 22:570–572.
  • Roy J-N, Lajoie J, Zijenah LS, et al. (2005). CYP3A5 genetic polymorphisms in different ethnic populations. Drug Metab Dispos33:884–887.
  • Saeki T, Ueda K, Tanigawara Y, et al. (1993). Human P-glycoprotein transports cyclosporin A and FK506. J Biol Chem 268:6077–6080.
  • Sakai M, Hobara N, Hokama N, et al. (2004). Increased bioavailability of tacrolimus after rectal administration in rats. Biol Pharm Bull 27:1480–1482.
  • Sakata A, Tamai I, Kawazu K, et al. (1994). In vivo evidence for ATP-dependent and P-glycoprotein-mediated transport of cyclosporin A at the blood-brain barrier. Biochem Pharmacol 48:1989–1992.
  • Sansone-Parsons A, Krishna G, Martinho M, et al. (2007). Effect of oral posaconazole on the pharmacokinetics of cyclosporine and tacrolimus. Pharmacotherapy 27:825–834.
  • Satoh H, Yamashita F, Tsujimoto M, et al. (2005). Citrus juices inhibit the function of human organic anion-transporting polypeptide OATP-B. Drug Metab Dispos 33:518–523.
  • Schinkel AH, Wagenaar E, van Deemter L, Mol CA, Borst P. (1995). Absence of the mdr1a P-Glycoprotein in mice affects tissue distribution and pharmacokinetics of dexamethasone, digoxin, and cyclosporin A. J Clin Invest 96:1698–1705.
  • Schmiedlin-Ren P, Edwards DJ, Fitzsimmons ME, et al. (1997). Mechanisms of enhanced oral availability of CYP3A4 substrates by grapefruit constituents. Decreased enterocyte CYP3A4 concentration and mechanism-based inactivation by furanocoumarins. Drug Metab. Dispos 25:1228–1233.
  • Scholten EM, Cremers SCLM, Schoemaker RC, et al. (2005). AUC-guided dosing of tacrolimus prevents progressive systemic overexposure in renal transplant recipients. Kidney Int 67:2440–2447.
  • Seelig A. (1998). A general pattern for substrate recognition by P-glycoprotein. Eur J Biochem 251:252–261.
  • Seelig A, Landwojtowicz E. (2000). Structure-activity relationship of P-glycoprotein substrates and modifiers. Eur J Pharm Sci 12:31–40.
  • Sheikh AM, Wolf DC, Lebovics E, et al. (1999). Concomitant human immunodeficiency virus protease inhibitor therapy markedly reduces tacrolimus metabolism and increases blood levels. Transplantation 68:307–309.
  • Shimomura M, Masuda S, Saito H, et al. (2002). Roles of the jejunum and ileum in the first-pass effect as absorptive barriers for orally administered tacrolimus. J Surg Res 103:215–222.
  • Shirasaka Y, Shichiri M, Mori T, et al. (2013). Major active components in grapefruit, orange, and apple juices responsible for OATP2B1-mediated drug interactions. J Pharm Sci 102:3418–3426.
  • Siddiqi N, Marfo K. (2010). Clinically significant drug-drug interaction between tacrolimus and phenobarbital: The price we pay. J Pharm Pract 23:585–589.
  • Singh D, Alexander J, Owen A, et al. (2004). Whole-blood cultures from renal-transplant patients stimulated ex vivo show that the effects of cyclosporine on lymphocyte proliferation are related to P-glycoprotein expression. Transplantation 77:557–561.
  • Sorkhi H, Moghadamnia AA, Oaliaee F, et al. (2009). Serum cyclosporine level and orange juice in pediatric renal-transplanted patients. Pediatr Transplant 13:411–413.
  • Spahn-Langguth H, Langguth P. (2001). Grapefruit juice enhances intestinal absorption of the P-glycoprotein substrate talinolol. Eur J Pharm Sci12:361–367.
  • Spriet I, Grootaert V, Meyfroidt G, et al. (2013). Switching from intravenous to oral tacrolimus and voriconazole leads to a more pronounced drug-drug interaction. Eur J Clin Pharmacol 69:737–738.
  • Sridar C, Goosen TC, Kent UM, et al. (2004). Silybin inactivates cytochromes P450 3A4 and 2C9 and inhibits major hepatic glucuronosyltransferases. Drug Metab Dispos 32:587–594.
  • Staatz C, Goodman L, Tett S. (2010a). Effect of CYP3A and ABCB1 single nucleotide polymorphisms on the pharmacokinetics and pharmacodynamics of calcineurin inhibitors: Part I. Clin Pharmacokinet 49:141–175.
  • Staatz CE, Goodman LK, Tett SE. (2010b). Effect of CYP3A and ABCB1 single nucleotide polymorphisms on the pharmacokinetics and pharmacodynamics of calcineurin inhibitors: Part II. Clin Pharmacokinet 49:207–221.
  • Staatz CE, Tett SE. (2004). Clinical pharmacokinetics and pharmacodynamics of tacrolimus in solid organ transplantation. Clinical Pharmacokinetics 43:623–653.
  • Staatz CE, Tett SE. (2005). Pharmacokinetic considerations relating to tacrolimus dosing in the elderly. Drugs Agin22:541–557.
  • Staatz CE, Willis C, Taylor PJ, et al. (2003). Toward better outcomes with tacrolimus therapy: Population pharmacokinetics and individualized dosage prediction in adult liver transplantation. Liver Transplant 9:130–137.
  • Staatz CE, Willis C, Taylor PJ, Tett SE. (2002). Population pharmacokinetics of tacrolimus in adult kidney transplant recipients. Clin Pharmacol Ther 72:660–669.
  • Storset E, Holford N, Hennig S, et al. (2014a). Improved prediction of tacrolimus concentrations early after kidney transplantation using theory-based pharmacokinetic modelling. Br J Clin Pharmacol 78:509–523.
  • Storset E, Holford N, Midtvedt K, et al. (2014b). Importance of hematocrit for a tacrolimus target concentration strategy. Eur J Clin Pharmacol 70:65–77.
  • Stratta P, Quaglia M, Cena T, et al. (2012). The interactions of age, sex, body mass index, genetics, and steroid weight-based doses on tacrolimus dosing requirement after adult kidney transplantation. Eur J Clin Pharmacol 68:671–680.
  • Strouse TB, Fairbanks LA, Skotzko CE, Fawzy FI. (1996). Fluoxetine and cyclosporine in organ transplantation. Failure to detect significant drug interactions or adverse clinical events in depressed organ recipients. Psychosomatics 37:23–30.
  • Sun M, Kingdom J, Baczyk D, et al. (2006). Expression of the multidrug resistance P-glycoprotein, (ABCB1 glycoprotein) in the human placenta decreases with advancing gestation. Placenta 27:602–609.
  • Takaya S, Iwatsuki S, Noguchi T, et al. (1989). The influence of liver dysfunction on cyclosporine pharmacokinetics – A comparison between 70 per cent hepatectomy and complete bile duct ligation in dogs. Jpn J Surg 19:49–56.
  • Tanigawara Y, Okamura N, Hirai M, et al. (1992). Transport of digoxin by human P-glycoprotein expressed in a porcine kidney epithelial cell line (LLC-PK1). J Pharmacol Exp Ther 263:840–845.
  • Tapirdamaz Ö, Hesselink DA, el Bouazzaoui S, et al. (2014). Genetic variance in ABCB1 and CYP3A5 does not contribute toward the development of chronic kidney disease after liver transplantation. Pharmacogenet Genomics 24:427–435.
  • Tavira B, Gomez J, Diaz-Corte C, et al. (2015). The donor ABCB1 (MDR-1) C3435T polymorphism is a determinant of the graft glomerular filtration rate among tacrolimus treated kidney transplanted patients. J Hum Genetics 60:273–276.
  • Terrazzino S, Quaglia M, Stratta P, et al. (2012). The effect of CYP3A5 6986A>G and ABCB1 3435C>T on tacrolimus dose-adjusted trough levels and acute rejection rates in renal transplant patients: a systematic review and meta-analysis. Pharmacogenet Genomics 22:642–645.
  • Thelen K, Dressman JB. (2009). Cytochrome P450-mediated metabolism in the human gut wall. J Pharm Pharmacol 61:541–558.
  • Thielke J, Martin J, Weber FL, et al. (1998). Pharmacokinetics of tacrolimus and cyclosporine in short-bowel syndrome. Liver Transplant Surg 4:432–434.
  • Thorn M, Finnstrom N, Lundgren S, et al. (2005). Cytochromes P450 and MDR1 mRNA expression along the human gastrointestinal tract. Br J Clin Pharmacol 60:54–60.
  • Thummel KE, O’shea D, Paine MF, et al. (1996). Oral first-pass elimination of midazolam involves both gastrointestinal and hepatic CYP3A-mediated metabolism. Clin Pharmacol Ther 59:491–502.
  • Thummel KE, Wilkinson GR. (1998). In vitro and in vivo drug interactions involving human CYP3A. Annu Rev Pharmacol Toxicol 38:389–430.
  • Tortorice KL, Heim-Duthoy KL, Awni WM, et al. (1990). The effects of calcium channel blockers on cyclosporine and its metabolites in renal transplant recipients. Ther Drug Monitor 12:321–328.
  • Trotter JF, Stolpman N, Wachs M, et al. (2002). Living donor liver transplant recipients achieve relatively higher immunosuppressant blood levels than cadaveric recipients. Liver Transplant 8:212–218.
  • Trull AK, Tan KK, Tan L, et al. (1995). Absorption of cyclosporin from conventional and new microemulsion oral formulations in liver transplant recipients with external biliary diversion. Br J Clin Pharmacol 39:627–631.
  • Tsunashima D, Kawamura A, Murakami M, et al. (2014). Assessment of tacrolimus absorption from the human intestinal tract: Open-label, randomized, 4-way crossover study. Clin Ther 36:748–759.
  • Tsunoda SM, Harris RZ, Christians U, et al. (2001). Red wine decreases cyclosporine bioavailability. Clin Pharmacol Ther 70:462–467.
  • Undre NA, Schäfer A. (1998). Factors affecting the pharmacokinetics of tacrolimus in the first year after renal transplantation. European Tacrolimus Multicentre Renal Study Group. Transplant Proc 30:1261–1263.
  • Urata K, Kawasaki S, Matsunami H, et al. (1995). Calculation of child and adult standard liver volume for liver transplantation. Hepatology (Baltimore, MD) 21:1317–1321.
  • van den Berg AP, Haagsma EB, Gouw AS, et al. (2001). Recurrent HCV infection reduces the requirement for tacrolimus after liver transplantation. Transplant Proc 33:1467.
  • Van Duijnhoven EM, Boots JMM, Christiaans MHL, et al. (2003). Increase in tacrolimus trough levels after steroid withdrawal. Transpl Int 16:721–725.
  • van Erp NPH, Baker SD, Zhao M, et al. (2005). Effect of milk thistle (Silybum marianum) on the pharmacokinetics of irinotecan. Clin Cancer Res 11:7800–7806.
  • van Hooff J, Van der Walt I, Kallmeyer J, et al. (2012). Pharmacokinetics in stable kidney transplant recipients after conversion from twice-daily to once-daily tacrolimus formulations. Ther Drug Monitor 34:46–52.
  • van der Pijl JW, Srivastava N, Denouel J, et al. (1996). Pharmacokinetics of the conventional and microemulsion formulations of cyclosporine in pancreas-kidney transplant recipients with gastroparesis. Transplantation 62:456–462.
  • von Richter O, Burk O, Fromm MF, et al. (2004). Cytochrome P450 3A4 and P-glycoprotein expression in human small intestinal enterocytes and hepatocytes: A comparative analysis in paired tissue specimens. Clin Pharmacol Ther 75:172–183.
  • Vasquez EM, Shin GP, Sifontis N, Benedetti E. (2005). Concomitant clotrimazole therapy more than doubles the relative oral bioavailability of tacrolimus. Ther Drug Monitor 27:587–591.
  • Vella JP, Sayegh MH. (1998). Interactions between cyclosporine and newer antidepressant medications. Am J Kidney Dis 31:320–323.
  • Venkataramanan R, Swaminathan A, Prasad T, et al. (1995). Clinical pharmacokinetics of tacrolimus. Clin Pharmacokinet 29:404–430.
  • Venkataramanan R, Zang S, Gayowski T, Singh N. (2002). Voriconazole inhibition of the metabolism of tacrolimus in a liver transplant recipient and in human liver microsomes. Antimicrob Agents Chemother 46:3091–3093.
  • Wada K, Takada M, Sakai M, et al. (2009). Drug interaction between tacrolimus and carbamazepine in a Japanese heart transplant recipient: A case report. J Heart Lung Transplant 28:409–411.
  • Wada K, Takada M, Ueda T, et al. (2007). Drug interactions between tacrolimus and phenytoin in Japanese heart transplant recipients: 2 Case reports. Int J Clin Pharmacol Ther 45:524–528.
  • Wandel C, Richard BK, Kajiji S, et al. (1999). P-Glycoprotein and cytochrome P-450 3A inhibition: Dissociation of inhibitory potencies. Cancer Res 59:3944–3948.
  • Wehland M, Bauer S, Brakemeier S, et al. (2011). Differential impact of the CYP3A5*1 and CYP3A5*3 alleles on pre-dose concentrations of two tacrolimus formulations. Pharmacogenet Genomics 21:179–184.
  • Wei-Lin W, Jing J, Shu-Sen Z, et al. (2006). Tacrolimus dose requirement in relation to donor and recipient ABCB1 and CYP3A5 gene polymorphisms in Chinese liver transplant patients. Liver Transplant 12:775–780.
  • Wentworth JM, Agostini M, Love J, et al. (2000). St John's wort, a herbal antidepressant, activates the steroid X receptor. J Endocrinol 166:R11–R16.
  • Willson TM, Kliewer SA. (2002). PXR, CAR and drug metabolism. Nat Rev Drug Discov 1:259–266.
  • Winkler M, Ringe B, Baumann J, et al. (1994). Plasma vs whole blood for therapeutic drug monitoring of patients receiving FK 506 for immunosuppression. Clin Chem 40:2247–2253.
  • Wlodarczyk Z, Squifflet J-P, Ostrowski M, et al. (2009). Pharmacokinetics for once- versus twice-daily tacrolimus formulations in de novo kidney transplantation: A randomized, open-label trial. Am J Transplant 9:2505–2513.
  • Wolffenbuttel L, Poli DD, Manfro RC, Goncalves LFS. (2004). Cyclosporine pharmacokinetics in anti-HCV + patients. Clin Transplant 18:654–660.
  • Woodhouse KW, Wynne HA. (1988). Age-related changes in liver size and hepatic blood flow. The influence on drug metabolism in the elderly. Clin Pharmacokinet 15:287–294.
  • Wright DH, Lake KD, Bruhn PS, Emery RWJ. (1999). Nefazodone and cyclosporine drug-drug interaction. J Heart Lung Transplant 18:913–915.
  • Wu J-W, Lin L-C, Hung S-C, et al. (2008). Hepatobiliary excretion of silibinin in normal and liver cirrhotic rats. Drug Metab Dispos 36:589–596.
  • Wu K-H, Cui Y-M, Guo J-F, et al. (2005). Population pharmacokinetics of cyclosporine in clinical renal transplant patients. Drug Metab Dispos33:1268–1275.
  • Wu X, Li Q, Xin H, et al. (2005). Effects of berberine on the blood concentration of cyclosporin A in renal transplanted recipients: Clinical and pharmacokinetic study. Eur J Clin Pharmacol 61:567–572.
  • Xin H-W, Li Q, Wu X-C, et al. (2011). Effects of Schisandra sphenanthera extract on the blood concentration of tacrolimus in renal transplant recipients. Eur J Clin Pharmacol 67:1309–1311.
  • Xu J, Go ML, Lim L-Y. (2003). Modulation of digoxin transport across Caco-2 cell monolayers by citrus fruit juices: Lime, lemon, grapefruit, and pummelo. Pharm Res 20:169–176.
  • Yamauchi A, Ieiri I, Kataoka Y, et al. (2002). Neurotoxicity induced by tacrolimus after liver transplantation: Relation to genetic polymorphisms of the ABCB1 (MDR1) gene. Transplantation 74:571–572.
  • Yamazaki H, Nakamoto M, Shimizu M, et al. (2010). Potential impact of cytochrome P450 3A5 in human liver on drug interactions with triazoles. Br J Clin Pharmacol 69:593–597.
  • Yanagimachi M, Naruto T, Tanoshima R, et al. (2010). Influence of CYP3A5 and ABCB1 gene polymorphisms on calcineurin inhibitor-related neurotoxicity after hematopoietic stem cell transplantation. Clin Transplant 24:855–861.
  • Yanagisawa R, Katsuyama Y, Shigemura T, et al. (2011). Engraftment syndrome, but not acute GVHD, younger age, CYP3A5 or MDR1 polymorphisms, increases tacrolimus clearance in pediatric hematopoietic SCT. Bone Marrow Transplant 46:90–97.
  • Yang CY, Chao PDL, Hou YC, et al. (2006). Marked decrease of cyclosporin bioavailability caused by coadministration of ginkgo and onion in rats. Food Chem Toxicol 44:1572–1578.
  • Yee GC, Stanley DL, Pessa LJ, et al. (1995). Effect of grapefruit juice on blood cyclosporin concentration. Lancet 345:955–956.
  • Yokogawa K, Takahashi M, Tamai I, et al. (1999). P-glycoprotein-dependent disposition kinetics of tacrolimus: Studies in mdr1a knockout mice. Pharm Res 16:1213–1218.
  • Yu KS, Cho JY, Jang IJ, et al. (2004). Effect of the CYP3A5 genotype on the pharmacokinetics of intravenous midazolam during inhibited and induced metabolic states. Clin Pharmacol Ther 76:104–112.
  • Zahir H, McCaughan C, Gleeson M, et al. (2004). Factors affecting variability in distribution of tacrolimus in liver transplant recipients. Br J Clin Pharmacol 57:298–309.
  • Zahir H, McLachlan AJ, Nelson A, et al. (2005). Population pharmacokinetic estimation of tacrolimus apparent clearance in adult liver transplant recipients. Ther Drug Monitor 27:422–430.
  • Zhang QY, Dunbar D, Ostrowska A, et al. (1999). Characterization of human small intestinal cytochromes P-450. Drug Metab Dispos 27:804–809.
  • Zhang W, Tan TMC, Lim LY. (2007). Impact of curcumin-induced changes in P-glycoprotein and CYP3A expression on the pharmacokinetics of peroral celiprolol and midazolam in rats. Drug Metab Dispos 35:110–115.
  • Zheng S, Easterling TR, Hays K, et al. (2013a). Tacrolimus placental transfer at delivery and neonatal exposure through breast milk. Br J Clin Pharmacol 76:988–996.
  • Zheng S, Easterling TR, Umans JG, et al. (2012a). Pharmacokinetics of tacrolimus during pregnancy. Ther Drug Monitor 34:660–670.
  • Zheng S, Tasnif Y, Hebert MF, et al. (2013b). CYP3A5 gene variation influences cyclosporine A metabolite formation and renal cyclosporine disposition. Transplantation 95:821–827.
  • Zheng S, Tasnif Y, Hebert MF, et al. (2012b). Measurement and compartmental modeling of the effect of CYP3A5 gene variation on systemic and intrarenal tacrolimus disposition. Clin Pharmacol Ther 92:737–745.
  • Zhou S-F, Xue CC, Yu X-Q, et al. (2007). Clinically important drug interactions potentially involving mechanism-based inhibition of cytochrome P450 3A4 and the role of therapeutic drug monitoring. Ther Drug Monitor 29:687–710.
  • Zhu L, Yang J, Zhang Y, et al. (2015). Effects of CYP3A5 genotypes, ABCB1 C3435T and G2677T/A polymorphism on pharmacokinetics of Tacrolimus in Chinese adult liver transplant patients. Xenobiotica 45:1–7.
  • Zylber-Katz E, Granot E. (2001). Abrupt increase of tacrolimus blood levels during an episode of Shigella infection in a child after liver transplantation. Ther Drug Monitor 23:647–649.

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