Effect of CYP3A5*3 genotypes on lumefantrine plasma concentrations among malaria-HIV-infected women

Abstract

Aim: We aimed to assess the effect of a functional polymorphism of CYP3A5 on lumefantrine pharmacokinetics. Patients & methods: Sixty-nine women diagnosed with malaria received standard doses of artemether–lumefantrine. Concentration–time data for lumefantrine and genotyping data were obtained for each participant. Pharmacokinetic-genotype associative relationships were assessed using linear regressions, Mann–Whitney U-test or Kruskal–Wallis statistics. Results: Average age and weight (standard deviation) of the patients were 33 (6.8) years and 59.5 (11.6) kg, respectively. CYP3A5*3 genotype associated with the log-transformed maximum concentration with the median (interquartile range) values of 8279 (6516–13,420) and 6331 (4093–8631) ng/ml (p = 0.032) among the carriers and noncarriers of CYP3A5*3, respectively. Besides, the NR1I3 c.152-1089T>C genotypes had an associative trend with the lumefantrine area under the curve (AUC0–96h) and clearance. Conclusion: CYP3A5*3 genetic variant is associated with a high maximum plasma concentration of lumefantrine. This warrants further investigations on the association between CYP3A5*3 gene variants, lumefantrine pharmacokinetics and electrophysiological effect.