Department of Pharmaceutical Chemistry, Obafemi Awolowo University, Ile Ife, Nigeria.
Pharmacogenomics. 2020 Dec;21(18):1289-1297. doi: 10.2217/pgs-2020-0081. Epub 2020 Nov 27.
We aimed to assess the effect of a functional polymorphism of CYP3A5 on lumefantrine pharmacokinetics. 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. Average age and weight (standard deviation) of the patients were 33 (6.8) years and 59.5 (11.6) kg, respectively. 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 , respectively. Besides, the c.152-1089T>C genotypes had an associative trend with the lumefantrine area under the curve (AUC) and clearance. *3 genetic variant is associated with a high maximum plasma concentration of lumefantrine. This warrants further investigations on the association between gene variants, lumefantrine pharmacokinetics and electrophysiological effect.
我们旨在评估 CYP3A5 功能多态性对青蒿琥酯药代动力学的影响。69 名被诊断患有疟疾的女性接受了标准剂量的青蒿琥酯-咯萘啶。为每位参与者获得了青蒿琥酯的浓度-时间数据和基因分型数据。使用线性回归、Mann-Whitney U 检验或 Kruskal-Wallis 统计评估药代动力学-基因型关联关系。患者的平均年龄和体重（标准差）分别为 33（6.8）岁和 59.5（11.6）kg。 与 基因型相关的是最大浓度的对数转换值，携带者和非携带者的中位数（四分位距）值分别为 8279（6516-13420）和 6331（4093-8631）ng/ml（p=0.032）。此外，c.152-1089T>C 基因型与青蒿琥酯 AUC 和清除率呈关联趋势。*3 遗传变异与青蒿琥酯的最高血浆浓度相关。这需要进一步研究基因变异、青蒿琥酯药代动力学和电生理效应之间的关系。
