1. Effect of CYP3A5 *3 genotypes on lumefantrine plasma concentrations among malaria-HIV-infected women.
- Author
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Adegbola AJ, Soyinka JO, and Bolaji OO
- Subjects
- Adolescent, Adult, Antimalarials therapeutic use, Area Under Curve, Artemether therapeutic use, Artemether, Lumefantrine Drug Combination, Constitutive Androstane Receptor, Drug Combinations, Female, Genotype, Humans, Lumefantrine therapeutic use, Malaria complications, Malaria drug therapy, Middle Aged, Polymorphism, Single Nucleotide, Young Adult, Antimalarials blood, Cytochrome P-450 CYP3A genetics, HIV Infections complications, Lumefantrine blood, Malaria metabolism
- 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 (AUC
0-96h ) 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.- Published
- 2020
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