Amodiaquine metabolism is impaired by common polymorphisms in CYP2C8: implications for malaria treatment in Africa.

摘要: Metabolism of the antimalarial drug amodiaquine (AQ) into its primary metabolite, N-desethylamodiaquine, is mediated by CYP2C8. We studied frequency CYP2C8 variants in 275 malaria-infected patients Burkina Faso, metabolism AQ variants, and impact other drugs on metabolism. The allele frequencies CYP2C8*2 CYP2C8*3 were 0.155 0.003, respectively. No evidence was seen for influence genotype efficacy or toxicity, but sample size limited these assessments. variant most common Africans, CYP2C8(*)2, showed defective (threefold higher K(m) sixfold lower intrinsic clearance), CYP2C8(*)3 had markedly decreased activity. Considering likely to be coadministered with AQ, antiretroviral efavirenz, saquinavir, lopinavir, tipranavir potent inhibitors at clinically relevant concentrations. Variable activity owing genetic variation interactions may have important clinical implications toxicity AQ.