The role of organic anion transporting polypeptides in drug absorption, distribution, excretion and drug-drug interactions

被引:60
作者
Kovacsics, Daniella [1 ]
Patik, Izabel [1 ]
Ozvegy-Laczka, Csilla [1 ]
机构
[1] Hungarian Acad Sci, Inst Enzymol, Membrane Prot Res Grp, Res Ctr Nat Sci, Budapest, Hungary
基金
匈牙利科学研究基金会;
关键词
Drug-drug interaction; hepatic clearance; intestinal absorption; organic anion transporting polypeptides; pharmacokinetics; pharmacogenetics; ADME; GWAS; HUMAN PROSTAGLANDIN TRANSPORTER; MESSENGER-RNA EXPRESSION; OATP-B SLC21A9; HEPATIC-UPTAKE; IN-VITRO; FUNCTIONAL-CHARACTERIZATION; GENETIC POLYMORPHISMS; SLCO1B1; POLYMORPHISM; PROSTATE-CANCER; CELLULAR UPTAKE;
D O I
10.1080/17425255.2017.1253679
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Introduction: The in vivo fate and effectiveness of a drug depends highly on its absorption, distribution, metabolism, excretion and toxicity (ADME-Tox). Organic anion transporting polypeptides (OATPs) are membrane proteins involved in the cellular uptake of various organic compounds, including clinically used drugs. Since OATPs are significant players in drug absorption and distribution, modulation of OATP function via pharmacotherapy with OATP substrates/inhibitors, or modulation of their expression, affects drug pharmacokinetics. Given their cancer-specific expression, OATPs may also be considered anticancer drug targets.Areas covered: We describe the human OATP family, discussing clinically relevant consequences of altered OATP function. We offer a critical analysis of published data on the role of OATPs in ADME and in drug-drug interactions, especially focusing on OATP1A2, 1B1, 1B3 and 2B1.Expert opinion: Four members of the OATP family, 1A2, 1B1, 1B3 and 2B1, have been characterized in detail. As biochemical and pharmacological knowledge on the other OATPs is lacking, it seems timely to direct research efforts towards developing the experimental framework needed to investigate the transport mechanism and substrate specificity of the poorly described OATPs. In addition, elucidating the role of OATPs in tumor development and therapy response are critical avenues for further research.
引用
收藏
页码:409 / 424
页数:16
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