Drug Transporters in Drug Efficacy and Toxicity

被引:259
作者
DeGorter, M. K. [1 ]
Xia, C. Q. [2 ]
Yang, J. J. [2 ]
Kim, R. B. [1 ]
机构
[1] Univ Western Ontario, Div Clin Pharmacol, London, ON N6A 5A5, Canada
[2] Millennium Pharmaceut Inc, Dept Drug Metab & Pharmacokinet, Cambridge, MA 02139 USA
来源
ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY, VOL 52 | 2012年 / 52卷
关键词
ATP-binding cassette transporters; solute carrier transporters; pharmacokinetics; pharmacogenetics; drug-drug interactions; transporter knockout mice; CANCER RESISTANCE PROTEIN; ORGANIC CATION TRANSPORTER; SINGLE NUCLEOTIDE POLYMORPHISMS; TOXIN EXTRUSION MATE1; BLOOD-BRAIN-BARRIER; OATP-C SLC21A6; MULTIDRUG-RESISTANCE; P-GLYCOPROTEIN; GENETIC-VARIATION; SLCO1B1; POLYMORPHISM;
D O I
10.1146/annurev-pharmtox-010611-134529
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Drug transporters are now widely acknowledged as important determinants governing drug absorption, excretion, and, in many cases, extent of drug entry into target organs. There is also a greater appreciation that altered drug transporter function, whether due to genetic polymorphisms, drug-drug interactions, or environmental factors such as dietary constituents, can result in unexpected toxicity. Such effects are in part due to the interplay between various uptake and efflux transporters with overlapping functional capabilities that can manifest as marked interindividual variability in drug disposition in vivo. Here we review transporters of the solute carrier (SLC) and ATP-binding cassette (ABC) superfamilies considered to be of major importance in drug therapy and outline how understanding the expression, function, and genetic variation in such drug transporters will result in better strategies for optimal drug design and tissue targeting as well as reduce the risk for drug-drug interactions and adverse drug responses.
引用
收藏
页码:249 / 273
页数:25
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