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Drug Metabolism Reviews Volume 55, 2023 - Issue 4
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Review Articles

Drug transporters in drug disposition – the year 2022 in review

Paresh P. Chothea Department of Drug Metabolism and Pharmacokinetics, Oncology Research and Development, AstraZeneca, Waltham, MA, USACorrespondence[email protected]
,
Pallabi Mitrab Department of Drug Metabolism and Pharmacokinetics, Boehringer Ingelheim Pharmaceuticals Inc, Ridgefield, CT, USA
,
Masanori Nakakariyac Drug Metabolism and Pharmacokinetics Research Laboratories, Takeda Pharmaceutical Company Limited, Fujisawa, Japan
,
Diane Ramsdena Department of Drug Metabolism and Pharmacokinetics, Oncology Research and Development, AstraZeneca, Waltham, MA, USA
,
Charles J. Rotterd Global Drug Metabolism and Pharmacokinetics, Takeda Development Center Americas, Inc. (TDCA), San Diego, CA, USA
,
Philip Sandovale Global Drug Metabolism and Pharmacokinetics, Takeda Development Center Americas, Inc. (TDCA), Lexington, MA, USA
&
Kimio Tohyamac Drug Metabolism and Pharmacokinetics Research Laboratories, Takeda Pharmaceutical Company Limited, Fujisawa, Japan
 show all
Pages 343-370 | Received 15 May 2023, Accepted 11 Aug 2023, Published online: 06 Sep 2023

References

  • Chothe PP, Mitra P, Nakakariya M, Ramsden D, Rotter CJ, Sandoval P, Tohyama K. 2022. Novel insights in drug transporter sciences: the year 2021 in review. Drug Metab Rev. 54(3):299–317. doi: 10.1080/03602532.2022.2094944
  • Chothe PP, Nakakariya M, Rotter CJ, Sandoval P, Tohyama K. 2021. Recent advances in drug transporter sciences: highlights from the year 2020. Drug Metab Rev. 53(3):321–349.

References

  • Bernd A, Ott M, Ishikawa H, Schroten H, Schwerk C, Fricker G. 2015. Characterization of efflux transport proteins of the human choroid plexus papilloma cell line HIBCPP, a functional in vitro model of the blood-cerebrospinal fluid barrier. Pharm Res. 32(9):2973–2982.
  • Ferrazzini G, Sohl H, Robieux I, Johnson D, Giesbrecht E, Koren G. 1991. Diurnal variation of methotrexate disposition in children with acute leukaemia. Eur J Clin Pharmacol. 41(5):425–427.
  • Gachon F, Firsov D. 2011. The role of circadian timing system on drug metabolism and detoxification. Expert Opin Drug Metab Toxicol. 7(2):147–158.
  • Guan D, Lazar MA. 2022. Circadian regulation of gene expression and metabolism in the liver. Semin Liver Dis. 42(2):113–121.
  • Hamdan AM, Koyanagi S, Wada E, Kusunose N, Murakami Y, Matsunaga N, Ohdo S. 2012. Intestinal expression of mouse Abcg2/breast cancer resistance protein (BCRP) gene is under control of circadian clock-activating transcription factor-4 pathway. J Biol Chem. 287(21):17224–17231.
  • Hastings MH, Maywood ES, Brancaccio M. 2018. Generation of circadian rhythms in the suprachiasmatic nucleus. Nat Rev Neurosci. 19(8):453–469.
  • Lu D, Wang Z, Wu B. 2022. Pharmacokinetics-based chronotherapy. Curr Drug Metab. 23(1):2–7.
  • Oh JH, Lee JH, Han DH, Cho S, Lee YJ. 2017. Circadian clock is involved in regulation of hepatobiliary transport mediated by multidrug resistance-associated protein 2. J Pharm Sci. 106(9):2491–2498. doi: 10.1016/j.xphs.2017.04.071.
  • Quintela T, Sousa C, Patriarca FM, Goncalves I, Santos CR. 2015. Gender associated circadian oscillations of the clock genes in rat choroid plexus. Brain Struct Funct. 220(3):1251–1262. doi: 10.1007/s00429-014-0720-1.
  • Stow LR, Gumz ML. 2011. The circadian clock in the kidney. J Am Soc Nephrol. 22(4):598–604.
  • Zhang YK, Yeager RL, Klaassen CD. 2009. Circadian expression profiles of drug-processing genes and transcription factors in mouse liver. Drug Metab Dispos. 37(1):106–115.

References

  • Chen Y, Ma F, Jones NS, Yoshida K, Chiang PC, Durk MR, Wright MR, Jin JY, Chinn LW. 2020. Physiologically-based pharmacokinetic model-informed drug development for fenebrutinib: understanding complex drug-drug interactions. CPT Pharmacomet Syst Pharmacol. 9(6):332–341.
  • Izumi S, Nozaki Y, Lee W, Sugiyama Y. 2022. Experimental and urrO pin evidence supporting the trans-inhibition mechanism for preincubation time-dependent, long-lasting inhibition of organic anion transporting polypeptide 1B1 by cyclosporine A. Drug Metab Dispos. 50(5):541–551.
  • Shitara Y, Takeuchi K, Nagamatsu Y, Wada S, Sugiyama Y, Horie T. 2012. Long-lasting inhibitory effects of cyclosporin A, but not tacrolimus, on OATP1B1- and OATP1B3-mediated uptake. Drug Metab Pharmacokinet. 27(4):368–378.

References

  • European Medicines Agency (EMA). 2012. Committee for Human Medicinal Products (CHMP): guideline on the Investigation of Drug Interactions. European Medicines Agency. https://www.ema.europa.eu/en/investigation-drug-interactions-scientific-guideline
  • Food and Drug Administration. 2020. Guidance for industry: in vitro drug interaction studies – cytochrome P450 enzyme- and transporter-mediated drug interactions. U. S. Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research (CDER). https://www.fda.gov/media/134582/download.
  • PMDA. 2019. Guideline on drug interaction for drug development and appropriate provision of information: English version. Ministry of Health, Labour and Welfare. [accessed 2019 February 8]. https://www.mhlw.go.jp/hourei/doc/tsuchi/T190212I0040.pdf.
  • Duan P, Zhao P, Zhang L. 2017. Physiologically based pharmacokinetic (PBPK) urrO pin of pitavastatin and atorvastatin to predict drug-drug interactions (DDIs). Eur J Drug Metab Pharmacokinet. 42(4):689–705.
  • Taskar KS, Pilla Reddy V, Burt H, Posada MM, Varma M, Zheng M, Ullah M, Emami Riedmaier A, Umehara KI, Snoeys J, et al. 2020. Physiologically-based pharmacokinetic models for evaluating membrane transporter mediated drug-drug interactions: current capabilities, case studies, future opportunities, and recommendations. Clin Pharmacol Ther. 107(5):1082–1115.
  • Kunze A, Ediage EN, Dillen L, Monshouwer M, Snoeys J. 2018. Clinical investigation of coproporphyrins as sensitive biomarkers to predict mild to strong OATP1B-mediated drug-drug interactions. Clin Pharmacokinet. 57(12):1559–1570.

References

  • Chang Y, Burckart GJ, Lesko LJ, Dowling TC. 2013. Evaluation of hepatic impairment dosing recommendations in FDA-approved product labels. J Clin Pharmacol. 53(9):962–966.
  • El-Khateeb E, Darwich AS, Achour B, Athwal V, Rostami-Hodjegan A. 2021. Review article: time to revisit Child-Pugh score as the basis for predicting drug clearance in hepatic impairment. Aliment Pharmacol Ther. 54(4):388–401.
  • Chu X, Prasad B, Neuhoff S, Yoshida K, Leeder JS, Mukherjee D, Taskar K, Varma MVS, Zhang X, Yang X, et al. 2022. Clinical implications of altered drug transporter abundance/function and PBPK urrO pin in specific populations: an ITC perspective. Clin Pharmacol Ther. 112(3):501–526.
  • Vildhede A, Kimoto E, Rodrigues AD, Varma MVS. 2018. Quantification of hepatic organic anion transport proteins OAT2 and OAT7 in human liver tissue and primary hepatocytes. Mol Pharm. 15(8):3227–3235.

References

  • Arya V, Reynolds KS, Yang X. 2022. Using endogenous biomarkers to derisk assessment of transporter-mediated drug-drug interactions: a scientific perspective. J Clin Pharmacol. 62(12):1501–1506.

References

  • Shitara Y, Sugiyama Y. 2017. Preincubation-dependent and long-lasting inhibition of organic anion transporting polypeptide (OATP) and its impact on drug-drug interactions. Pharmacol Ther. 177:67–80.
  • Mochizuki T, Zamek‐Gliszczynski MJ, Yoshida K, Mao J, Taskar K, Hirabayashi H, Chu X, Lai Y, Takashima T, Rockich K, et al. 2022. Effect of cyclosporin A and impact of dose staggering on OATP1B1/1B3 endogenous substrates and drug probes for assessing clinical drug interactions. Clin Pharmacol Ther. 111(6):1315–1323.

References

  • Kumar V, Yin M, Ishida K, Salphati L, Hop C, Rowbottom C, Xiao G, Lai Y, Mathias A, Chu X, et al. 2021. Prediction of transporter-mediated rosuvastatin hepatic uptake clearance and drug interaction in humans using proteomics-informed REF approach. Drug Metab Dispos. 49(2):159–168.
  • Sachar M, Kumar V, Gormsen LC, Munk OL, Unadkat JD. 2020. Successful prediction of positron emission tomography-imaged metformin hepatic uptake clearance in humans using the quantitative proteomics-informed relative expression factor approach. Drug Metab Dispos. 48(11):1210–1216.

References

  • Saleeb RM, Brimo F, Farag M, Rompre-Brodeur A, Rotondo F, Beharry V, Wala S, Plant P, Downes MR, Pace K, et al. 2017. Toward biological subtyping of papillary renal cell carcinoma with clinical implications through histologic, immunohistochemical, and molecular analysis. Am J Surg Pathol. 41(12):1618–1629.
  • Saleeb RM, Plant P, Tawedrous E, Krizova A, Brimo F, Evans AJ, Wala SJ, Bartlett J, Ding Q, Boles D, et al. 2018. Integrated phenotypic/genotypic analysis of papillary renal cell carcinoma subtypes: identification of prognostic markers, cancer-related pathways, and implications for therapy. Eur Urol Focus. 4(5):740–748.
  • Suzuki H, Sugiyama Y. 2002. Single nucleotide polymorphisms in multidrug resistance associated protein 2 (MRP2/ABCC2): its impact on drug disposition. Adv Drug Deliv Rev. 54(10):1311–1331.
  • Wada M, Toh S, Taniguchi K, Nakamura T, Uchiumi T, Kohno K, Yoshida I, Kimura A, Sakisaka S, Adachi Y, et al. 1998. Mutations in the urrO pin r multispecific organic anion transporter (cMOAT) gene, a novel ABC transporter, in patients with hyperbilirubinemia II/Dubin-Johnson syndrome. Hum Mol Genet. 7(2):203–207.
  • Yacovino LL, Gibson CJ, Aleksunes LM. 2013. Down-regulation of brush border efflux transporter expression in the kidneys of pregnant mice. Drug Metab Dispos. 41(2):320–325.

References

  • FDA. 2020. In vitro drug interaction studies—cytochrome P450 enzyme- and transporter-mediated drug interactions guidance for industry. Washington: FDA.
  • 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(5):1260–1287. doi: 10.1111/j.1476-5381.2011.01724.x.

References

  • Ambudkar SV, Kimchi-Sarfaty C, Sauna ZE, Gottesman MM. 2003. P-glycoprotein: from genomics to mechanism. Oncogene. 22(47):7468–7485.
  • Fletcher JI, Williams RT, Henderson MJ, Norris MD, Haber M. 2016. ABC transporters as mediators of drug resistance and contributors to cancer cell biology. Drug Resist Updat. 26:1–9.
  • Neklesa TK, Winkler JD, Crews CM. 2017. Targeted protein degradation by PROTACs. Pharmacol Ther. 174:138–144.
  • Shirasaki R, Matthews GM, Gandolfi S, de Matos Simoes R, Buckley DL, Raja Vora J, Sievers QL, Bruggenthies JB, Dashevsky O, Poarch H, et al. 2021. Functional genomics identify distinct and overlapping genes mediating resistance to different classes of heterobifunctional degraders of oncoproteins. Cell Rep. 34(1):108532.

References

  • Brunk E, Sahoo S, Zielinski DC, Altunkaya A, Drager A, Mih N, Gatto F, Nilsson A, Preciat Gonzalez GA, Aurich MK, et al. 2018. Recon3D enables a three-dimensional view of gene variation in human metabolism. Nat Biotechnol. 36(3):272–281.
  • Nigam SK, Bhatnagar V. 2018. The systems biology of uric acid transporters: the role of remote sensing and signaling. urrO pin Nephrol Hypertens. 27(4):305–313.
  • Ingraham L, Li M, Renfro JL, Parker S, Vapurcuyan A, Hanna I, Pelis RM. 2014. A plasma concentration of alpha-ketoglutarate influences the kinetic interaction of ligands with organic anion transporter 1. Mol Pharmacol. 86(1):86–95.
  • Jansen J, Jansen K, Neven E, Poesen R, Othman A, van Mil A, Sluijter J, Sastre Torano J, Zaal EA, Berkers CR, et al. 2019. Remote sensing and signaling in kidney proximal tubules stimulates gut microbiome-derived organic anion secretion. Proc Natl Acad Sci USA. 116(32):16105–16110. doi: 10.1073/pnas.1821809116.

References

  • Aitken AE, Richardson TA, Morgan ET. 2006. Regulation of drug-metabolizing enzymes and transporters in inflammation. Annu Rev Pharmacol Toxicol. 46:123–149. doi:10.1146/annurev.pharmtox.46.120604.141059.
  • Billington S, Ray AS, Salphati L, Xiao G, Chu X, Humphreys WG, Liao M, Lee CA, Mathias A, Hop C, et al. 2018. Transporter expression in noncancerous and cancerous liver tissue from donors with hepatocellular carcinoma and chronic hepatitis C infection quantified by LC-MS/MS proteomics. Drug Metab Dispos. 46(2):189–196.
  • Cobbina E, Akhlaghi F. 2017. Non-alcoholic fatty liver disease (NAFLD) - pathogenesis, classification, and effect on drug metabolizing enzymes and transporters. Drug Metab Rev. 49:197–211.
  • Drozdzik M, Szelag-Pieniek S, Post M, Zeair S, Wrzesinski M, Kurzawski M, Prieto J, Oswald S. 2020. Protein abundance of hepatic drug transporters in patients with different forms of liver damage. Clin Pharmacol Ther. 107(5):1138–1148. doi: 10.1002/cpt.1717.
  • Eley T, Han YH, Huang SP, He B, Li W, Bedford W, Stonier M, Gardiner D, Sims K, Rodrigues AD, et al. 2015. Organic anion transporting polypeptide-mediated transport of, and inhibition by, asunaprevir, an inhibitor of hepatitis C virus NS3 protease. Clin Pharmacol Ther. 97(2):159–166.
  • El-Khateeb E, Achour B, Al-Majdoub ZM, Barber J, Rostami-Hodjegan A. 2021. Non-uniformity of changes in drug-metabolizing enzymes and transporters in liver cirrhosis: implications for drug dosage adjustment. Mol Pharm. 18(9):3563–3577.
  • Wang L, Collins C, Kelly EJ, Chu X, Ray AS, Salphati L, Xiao G, Lee C, Lai Y, Liao M, et al. 2016. Transporter expression in liver tissue from subjects with alcoholic or hepatitis C cirrhosis quantified by targeted quantitative proteomics. Drug Metab Dispos. 44(11):1752–1758.

References

  • Bednarczyk D. 2021. Passive influx and ion trapping are more relevant to the cellular accumulation of highly permeable low-molecular-weight acidic drugs than is organic anion transporter 2. Drug Metab Dispos. 49(8):648–657.
  • Bi YA, Mathialagan S, Tylaska L, Fu M, Keefer J, Vildhede A, Costales C, Rodrigues AD, Varma MVS. 2018. Organic anion transporter 2 mediates hepatic uptake of tolbutamide, a CYP2C9 Probe Drug. J Pharmacol Exp Ther. 364(3):390–398. doi: 10.1124/jpet.117.245951.
  • Cropp CD, Komori T, Shima JE, Urban TJ, Yee SW, More SS, Giacomini KM. 2008. Organic anion transporter 2 (SLC22A7) is a facilitative transporter of cGMP. Mol Pharmacol. 73(4):1151–1158.
  • Danielson ML, Sawada GA, Raub TJ, Desai PV. 2018. In silico and in vitro assessment of OATP1B1 inhibition in drug discovery. Mol Pharm. 15(8):3060–3068.
  • Kimoto E, Mathialagan S, Tylaska L, Niosi M, Lin J, Carlo AA, Tess DA, Varma MVS. 2018. Organic anion transporter 2-mediated hepatic uptake contributes to the clearance of high-permeability-low-molecular-weight acid and zwitterion drugs: evaluation using 25 drugs. J Pharmacol Exp Ther. 367(2):322–334.
  • Nigam SK, Bush KT, Martovetsky G, Ahn SY, Liu HC, Richard E, Bhatnagar V, Wu W. 2015. The organic anion transporter (OAT) family: a systems biology perspective. Physiol Rev. 95(1):83–123.
  • Weaver YM, Hagenbuch B. 2010. Several conserved positively charged amino acids in OATP1B1 are involved in binding or translocation of different substrates. J Membr Biol. 236(3):279–290.
  • Zamek-Gliszczynski MJ, Sangha V, Shen H, Feng B, Wittwer MB, Varma MVS, Liang X, Sugiyama Y, Zhang L, Bendayan R. 2022. Transporters in drug development: international transporter consortium update on emerging transporters of clinical importance. Clin Pharma and Therapeutics. 112(3):485–500. doi: 10.1002/cpt.2644.

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