Polymorphism drug transporter

Other examples of polymorphic drug transporter proteins include the dipeptide transporter, organic anion and cation transporters, and L-amino acid transporter. Their effects on drug distribution are the focus of ongoing research. 

Ishikawa, T., Onishi, Y., Hirano, H. et al. (2004). Pharmacogenomics of drug transporters a new approach to functional analysis of the genetic polymorphisms of ABCB1 (P-glycoprotein/MDRl). Biol. Pharm. Bull., 27, 939 48. 

Brinkmann, U., Eichelbaum, M., Polymorphisms in the ABC drug transporter gene MDR1, Pharmacogenomics J. 2001, 3, 59-64. 

As SNP discovery technologies become mainstream research tools, the importance of genotype-phenotype relationships will continue to be a focus in pharma-cogenomic research. Not only will characterization of drug transporter polymorphisms enhance our insight of the molecular mechanisms involved in transporter function, it is likely that such findings will become important components of individualized drug therapy in the future. 

Interestingly, these assays have been employed to address the functional consequences of polymorphisms in the ABCC family of transporters but no notable alterations in transport capacity have been found (43). It seems that although ABCC transporters contain several potentially important polymorphisms and are important in drug transport overall, functional variability is actually quite low. This is perhaps the reason for the multiple negative studies that have assessed ABCC polymorphisms as they relate to drug bioavailability (20). 

Nozawa, T., Minami, H., Sugiura, S., Tsuji, A., and Tamai, 1. (2005) Role of organic anion transporter OATPIBI (OATP-C) in hepatic uptake of irinotecan and its active metabolite, 7-ethyl-10-hydroxycamptothecin in vitro evidence and effect of single nucleotide polymorphisms. Drug Metab. Dispos. 33, 434—439. 

Cascorbi, I., Gerloff, T., Johne, A., et al. (2001) Erequency of single nucleotide polymorphisms in the P-glycoprotein drug transporter MDRl gene in white subjects. Clin. Pharmacol. Ther. 69, 169-174. 

Siddiqui A et al Association of multidrug resistance in epilepsy with a polymorphism in the drug-transporter gene ABCB1. N Engl J Med 2002 348 15. 

Bosch TM, Meijerman I, Beijnen JH, Schellens JH. Genetic polymorphisms of drug-metabolising enzymes and drug transporters in the chemotherapeutic treatment of cancer. Clin Pharmacokinet. 2006 45 253-285. 

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