alexa Minimal effect of MDR1 and CYP3A5 genetic polymorphisms on the pharmacokinetics of indinavir in HIV-infected patients.


Journal of Clinical & Experimental Dermatology Research

Author(s): Solas C, Simon N, Drogoul MP, Quaranta S, FrixonMarin V,

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Abstract AIMS: The protease inhibitor indinavir is characterized by an important interindividual pharmacokinetic variability, which results from the actions of the metabolizing enzymes cytochrome P450 (CYP) 3A and the multidrug efflux pump P-glycoprotein (P-gp), encoded by MDR1. Using a population pharmacokinetic approach, we investigated the effect of several MDR1 and CYP3A5 polymorphisms on the pharmacokinetic parameters of indinavir in HIV-infected patients. METHODS: Twenty-eight patients receiving indinavir alone or together with ritonavir were included. Indinavir pharmacokinetics were studied over a 12 h interval. Genetic polymorphisms were assessed by real-time PCR assays and direct sequencing for MDR1 and by PCR-SSCP analysis for CYP3A5. RESULTS: The pharmacokinetics of indinavir were best described by a one-compartment model with first-order absorption. In the final model, the MDR1 C3435T genotype and ritonavir were identified as statistically significant covariates (P This article was published in Br J Clin Pharmacol and referenced in Journal of Clinical & Experimental Dermatology Research

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