Differential impact of nevirapine on artemether-lumefantrine pharmacokinetics in individuals stratified by CYP2B6 c.516G>T genotypes

There is an increased recognition of the need to identify and quantify the impact of genetic polymorphisms on drug-drug interactions. This study investigated the pharmacogenetics of the pharmacokinetic drug-drug interaction between nevirapine and artemether-lumefantrine in HIV-positive and HIV-negative adult Nigerian subjects. Thirty each of HIV-infected patients on nevirapine-based antiretroviral therapy and HIV-negative volunteers without clinical malaria, but with predetermined CYP2B6 c.516GG and TT genotypes were administered a complete treatment dose of 3-days of artemether-lumefantrine. Rich pharmacokinetic sampling prior to and following the last dose was conducted and plasma concentrations of artemether/dihydroartemisinin and, lumefantrine/desbutyl-lumefantrine were quantified using tandem mass spectrometry. Pharmacokinetic parameters of artemether-lumefantrine and its metabolites in HIV-infected patients on nevirapine were compared with those in the absence of nevirapine in HIV...