Accumulating evidence strongly suggests that genetic polymorphisms in drug-metabolizing enzymes, transporters, receptors, and other drug targets are linked to inter-individual differences in the efficacy and toxicity of many medications. During past two decades, the role of carrier-mediated transport in determining the pharmacokinetics of drugs has becoming increasingly evident with the discovery of genetic variants that affect expression and/or function of a given drug transporter. Drug transporters are expressed at numerous epithelial barriers, such as intestinal epithelial cells, hepatocytes, renal tubular cells and at the blood-brain barrier. Pharmacogenomic studies are rapidly elucidating the inherited nature of differences in pharmacokinetic and pharmacodynamic effects, thereby enhancing drug discovery and providing a stronger scientific basis for optimizing drug therapy on the basis of each patientâs genetic constitution. Hitherto researchers have associated alterations in drug uptake and/or disposition with the presence of genetic polymorphisms. The International Transporter Consortium (ITC) has most recently published the FDA Whitepaper as a report from the FDA Critical Path Initiative-sponsored Drug Transporter Workshop. The pharmaceutical regulatory authorities are now requesting that drug companies integrate genetic information into their clinical trial design. Toshihisa Ishikawa, Pharmacogenomics of drug transporters and clinical applications.
Last date updated on June, 2014