Development of Human Membrane Transporters: Drug Disposition and Pharmacogenetics

Overview

Journal Clin Pharmacokinet

Specialty Pharmacology

Date 2015 Sep 28

PMID 26410689

Citations 26

Authors

Miriam G Mooij

Anne T Nies

Catherijne A J Knibbe

Elke Schaeffeler

Dick Tibboel

Matthias Schwab

Saskia N de Wildt

Affiliations

Soon will be listed here.

Abstract

Membrane transporters play an essential role in the transport of endogenous and exogenous compounds, and consequently they mediate the uptake, distribution, and excretion of many drugs. The clinical relevance of transporters in drug disposition and their effect in adults have been shown in drug-drug interaction and pharmacogenomic studies. Little is known, however, about the ontogeny of human membrane transporters and their roles in pediatric pharmacotherapy. As they are involved in the transport of endogenous substrates, growth and development may be important determinants of their expression and activity. This review presents an overview of our current knowledge on human membrane transporters in pediatric drug disposition and effect. Existing pharmacokinetic and pharmacogenetic data on membrane substrate drugs frequently used in children are presented and related, where possible, to existing ex vivo data, providing a basis for developmental patterns for individual human membrane transporters. As data for individual transporters are currently still scarce, there is a striking information gap regarding the role of human membrane transporters in drug therapy in children.

Citing Articles

From Drug Discovery to Drug Approval: A Comprehensive Review of the Pharmacogenomics Status Quo with a Special Focus on Egypt.

Elgarhy F, Borham A, Alziny N, AbdElaal K, Shuaib M, Musaibah A Pharmaceuticals (Basel). 2024; 17(7).

PMID: 39065732 PMC: 11279872. DOI: 10.3390/ph17070881.

Understanding adefovir pharmacokinetics as a component of a transporter phenotyping cocktail.

Dong Q, Chen C, Taubert M, Bilal M, Kinzig M, Sorgel F Eur J Clin Pharmacol. 2024; 80(7):1069-1078.

PMID: 38546841 PMC: 11156719. DOI: 10.1007/s00228-024-03673-x.

Challenges of pediatric pharmacotherapy: A narrative review of pharmacokinetics, pharmacodynamics, and pharmacogenetics.

Watanabe H, Nagano N, Tsuji Y, Noto N, Ayusawa M, Morioka I Eur J Clin Pharmacol. 2023; 80(2):203-221.

PMID: 38078929 DOI: 10.1007/s00228-023-03598-x.

Lactobacillus plantarum-derived metabolites sensitize the tumor-suppressive effects of butyrate by regulating the functional expression of SMCT1 in 5-FU-resistant colorectal cancer cells.

Kim H, An J, Ha E J Microbiol. 2021; 60(1):100-117.

PMID: 34964946 DOI: 10.1007/s12275-022-1533-1.

Genetic variation of ABCB1 (rs1128503, rs1045642) and CYP2E1 rs3813867 with the duration of tuberculosis therapy: a pilot study among tuberculosis patients in Indonesia.

Barliana M, Kusuma A, Insani W, Alfian S, Diantini A, Mutakin M BMC Res Notes. 2021; 14(1):295.

PMID: 34332626 PMC: 8325820. DOI: 10.1186/s13104-021-05711-8.

References

Emami Riedmaier A, Nies A, Schaeffeler E, Schwab M . Organic anion transporters and their implications in pharmacotherapy. Pharmacol Rev. 2012; 64(3):421-49. DOI: 10.1124/pr.111.004614. View

Konieczna A, Erdosova B, Lichnovska R, Jandl M, cizkova K, Ehrmann J . Differential expression of ABC transporters (MDR1, MRP1, BCRP) in developing human embryos. J Mol Histol. 2011; 42(6):567-74. DOI: 10.1007/s10735-011-9363-1. View

Kell D, Dobson P, Oliver S . Pharmaceutical drug transport: the issues and the implications that it is essentially carrier-mediated only. Drug Discov Today. 2011; 16(15-16):704-14. DOI: 10.1016/j.drudis.2011.05.010. View

Chen H, Chen H, Liu Y, Feng C, Wu C, Shyu M . Developmental expression of canalicular transporter genes in human liver. J Hepatol. 2005; 43(3):472-7. DOI: 10.1016/j.jhep.2005.02.030. View

Fukudo M, Yano I, Masuda S, Goto M, Uesugi M, Katsura T . Population pharmacokinetic and pharmacogenomic analysis of tacrolimus in pediatric living-donor liver transplant recipients. Clin Pharmacol Ther. 2006; 80(4):331-45. DOI: 10.1016/j.clpt.2006.06.008. View

Fukuda T, Goebel J, Cox S, Maseck D, Zhang K, Sherbotie J . UGT1A9, UGT2B7, and MRP2 genotypes can predict mycophenolic acid pharmacokinetic variability in pediatric kidney transplant recipients. Ther Drug Monit. 2012; 34(6):671-9. PMC: 3498586. DOI: 10.1097/FTD.0b013e3182708f84. View

Allegaert K, Anderson B, Verbesselt R, Debeer A, de Hoon J, Devlieger H . Tramadol disposition in the very young: an attempt to assess in vivo cytochrome P-450 2D6 activity. Br J Anaesth. 2005; 95(2):231-9. DOI: 10.1093/bja/aei170. View

Hedman M, Neuvonen P, Neuvonen M, Antikainen M . Pharmacokinetics and pharmacodynamics of pravastatin in children with familial hypercholesterolemia. Clin Pharmacol Ther. 2003; 74(2):178-85. DOI: 10.1016/S0009-9236(03)00153-X. View

Giacomini K, Huang S, Tweedie D, Benet L, Brouwer K, Chu X . Membrane transporters in drug development. Nat Rev Drug Discov. 2010; 9(3):215-36. PMC: 3326076. DOI: 10.1038/nrd3028. View

10.

Emami-Riedmaier A, Schaeffeler E, Nies A, Morike K, Schwab M . Stratified medicine for the use of antidiabetic medication in treatment of type II diabetes and cancer: where do we go from here?. J Intern Med. 2014; 277(2):235-247. DOI: 10.1111/joim.12330. View

11.

Ziemniak J, Wynn R, Aranda J, Zarowitz B, Schentag J . The pharmacokinetics and metabolism of cimetidine in neonates. Dev Pharmacol Ther. 1984; 7(1):30-8. DOI: 10.1159/000457141. View

12.

van den Anker J, Schwab M, Kearns G . Developmental pharmacokinetics. Handb Exp Pharmacol. 2011; 205:51-75. DOI: 10.1007/978-3-642-20195-0_2. View

13.

Treiber A, Schneiter R, Hausler S, Stieger B . Bosentan is a substrate of human OATP1B1 and OATP1B3: inhibition of hepatic uptake as the common mechanism of its interactions with cyclosporin A, rifampicin, and sildenafil. Drug Metab Dispos. 2007; 35(8):1400-7. DOI: 10.1124/dmd.106.013615. View

14.

Ramsey L, Panetta J, Smith C, Yang W, Fan Y, Winick N . Genome-wide study of methotrexate clearance replicates SLCO1B1. Blood. 2012; 121(6):898-904. PMC: 3567337. DOI: 10.1182/blood-2012-08-452839. View

15.

Ramsey L, Bruun G, Yang W, Trevino L, Vattathil S, Scheet P . Rare versus common variants in pharmacogenetics: SLCO1B1 variation and methotrexate disposition. Genome Res. 2011; 22(1):1-8. PMC: 3246196. DOI: 10.1101/gr.129668.111. View

16.

Whirl-Carrillo M, McDonagh E, Hebert J, Gong L, Sangkuhl K, Thorn C . Pharmacogenomics knowledge for personalized medicine. Clin Pharmacol Ther. 2012; 92(4):414-7. PMC: 3660037. DOI: 10.1038/clpt.2012.96. View

17.

Nies A, Koepsell H, Damme K, Schwab M . Organic cation transporters (OCTs, MATEs), in vitro and in vivo evidence for the importance in drug therapy. Handb Exp Pharmacol. 2010; (201):105-67. DOI: 10.1007/978-3-642-14541-4_3. View

18.

Mooij M, Schwarz U, de Koning B, Leeder J, Gaedigk R, Samsom J . Ontogeny of human hepatic and intestinal transporter gene expression during childhood: age matters. Drug Metab Dispos. 2014; 42(8):1268-74. PMC: 4109212. DOI: 10.1124/dmd.114.056929. View

19.

Gong L, Stamer U, Tzvetkov M, Altman R, Klein T . PharmGKB summary: tramadol pathway. Pharmacogenet Genomics. 2014; 24(7):374-80. PMC: 4100774. DOI: 10.1097/FPC.0000000000000057. View

20.

Hines R . Developmental expression of drug metabolizing enzymes: impact on disposition in neonates and young children. Int J Pharm. 2012; 452(1-2):3-7. DOI: 10.1016/j.ijpharm.2012.05.079. View