This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The CYP3A4 and CYP3A5 are the most abundant CYP3A enzymes in adult human liver and small intestine, and are responsible for metabolism of more than 50% of all drugs. Substantial interindividual differences in CYP3A activity contribute greatly to variation in oral bioavailability and systemic clearance of CYP3A substrates. Genetic variation is one of the major factors that contribute to the interindividual variability. Recently, several common CYP3A5 gene variants, which determine the expression level and activity of CYP3A5, have been identified and could determine individual susceptibility to drug interactions. Since verapamil differentially inhibits CYP3A4 and CYP3A5, we plan to study the association between CYP3A5 genotypes and verapamil-mediated drug interactions.
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