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Influence of p-glycoprotein on the transport and metabolism of indinavir in caco-2 cells expressing cytochrome P-4503A4. J Pharmacol Exp Ther 2000; 292: 310–318

By Jerome H. Hochman, Masato Chiba, Joy Nishime, Masayo Yamazaki and Jiunn H. Lin


Caco-2 cells grown in the presence of 1a,25-di-OH vitamin D3 (di-OH vit D3) were used as a model to evaluate the effects of P-glycoprotein (Pgp) efflux on CYP3A4-mediated metabolism of indinavir during intestinal absorption. Caco-2 cells grown under these conditions demonstrated significant CYP3A4 ac-tivity and maintained Pgp-mediated directional transport of indinavir. Metabolism of indinavir in the di-OH vit D3-treated cells correlated with the level of CYP3A activity and generated metabolites consistent with CYP3A4-mediated metabolism. During transport experiments, indinavir metabolites are selec-tively secreted into the apical compartment, consistent with Pgp-mediated efflux. Using formation of the most abundant metabolite, M6, as a marker for indinavir metabolism, we ob-served that the extent of indinavir metabolism is not signifi

Year: 2016
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