Drug Transporter Function--Implications in CKD

Drug transporters typically move substrates, including drugs, in an intracellular to extracellular direction and thus are efflux transporters. There is a small subset of transporters that move substrates in the opposite direction and are classified as influx transporters. Collectively, drug transporters contribute to the pharmacokinetic profile of a wide variety of drugs and other molecules including xenobiotics, metabolites, and endogenous solutes. Identification of genetic variants in the genes that encode these transporters is an emerging area of pharmacogenomics. Many polymorphisms of the multitude of genes that code for the transporters within the 2 major superfamilies (ATP-binding cassette transporters and solute carrier transporters) have been identified. Studies have shown that many single-nucleotide polymorphisms are associated with changes in protein expression, functionality, and drug exposure; however, there are limited data for most single-nucleotide polymorphisms and impact on clinical end points. Preliminary data suggest that patients with CKD may have reduced transporter function that may have effects on exposure and toxicity profiles. Additional research translating the functional significance of polymorphisms on clinical pharmacokinetics and relevant disease-specific end points will provide further understanding of the role of genetic variations in transporter genes.