评价洛匹那韦利托那韦对尼日利亚拉各斯大学教学医院 HIV 感染者中盐酸左旋咪唑的药代动力学的影响。
Evaluation of the effects of atazanavir-ritonavir on the pharmacokinetics of lumefantrine in patients living with HIV in Lagos University Teaching Hospital, South-Western Nigeria.
机构信息
Department of Pharmacology, Therapeutics and Toxicology, College of Medicine of the University of Lagos, Idi-Araba, Lagos State, Nigeria.
Lagos University Teaching Hospital, Lagos, Nigeria.
出版信息
Eur J Clin Pharmacol. 2021 Sep;77(9):1341-1348. doi: 10.1007/s00228-021-03116-x. Epub 2021 Mar 23.
PURPOSE
Atazanavir-ritonavir (ATVr)-based antiretroviral therapy and artemether-lumefantrine (AL) are commonly used drugs for the treatment of human immune deficiency virus (HIV) infection and malaria respectively. However, interaction of both drugs, with Cytochrome P 3A4 (CYP 3A4) isoenzyme, may spawn clinically significant pharmacokinetic interactions. This study evaluated the effects of atazanavir-ritonavir on the pharmacokinetics of lumefantrine.
METHOD
In a case-control study, twenty participants having Plasmodium falciparum malaria were recruited and divided into two groups (ATVr-arm, n=10; and control-arm, n= 10). All the participants were administered six oral doses of AL 80-480 mg (Coartem). Thereafter, their blood samples were collected at different time intervals over seven days. The concentration of lumefantrine in each sample was quantified with high-performance liquid chromatography (HPLC) and used to determine its pharmacokinetic parameters which were compared between the test and control groups.
RESULTS
ATVr increased the mean day 7 concentration of lumefantrine (ATVr 3847.09 ± 893.35 ng/mL, control 1374.53 ± 265.55 ng/mL, p = 0.016) and the area under its plasma concentration-time curve (ATVr 670529.57 ± 157172.93 ng.h/mL, control 447976.28 ± 80886.99 ng.h/mL, p = 0.224) by 179.88 % and 49.68 %, respectively, but decreased its mean maximum plasma drug concentration (Cmax) (ATVr 13725.70 ± 2658.44 ng/mL, control 15380.48 ± 2332.62 ng/mL, p = 0.645) by 10.76 %.
CONCLUSION
ATVr increased drug exposure and day 7 plasma concentration of lumefantrine. AL is therefore considered effective for the treatment of malaria in patients taking ATVr-based regimen. However, the safety associated with the interaction requires further elucidation.
TRIAL REGISTRATION
Clin ClinicalTrials.gov Identifier: NCT04531072, August 27, 2020. "Retrospectively registered".
目的
阿扎那韦-利托那韦（ATVr）为抗逆转录病毒治疗药物，青蒿琥酯-咯萘啶（AL）为治疗人类免疫缺陷病毒（HIV）感染和疟疾的常用药物。然而，由于两者均经细胞色素 P 3A4（CYP 3A4）同工酶代谢，可能会产生具有临床意义的药物相互作用。本研究旨在评估阿扎那韦-利托那韦对咯萘啶药代动力学的影响。
方法
在一项病例对照研究中，招募了 20 名患有恶性疟原虫疟疾的参与者，并将其分为两组（ATVr 组，n=10；对照组，n=10）。所有参与者均接受了六次口服 AL 80-480mg（科泰复）。此后，在七天的不同时间间隔采集其血样。采用高效液相色谱法（HPLC）定量检测每个样本中咯萘啶的浓度，并用于比较两组间的药代动力学参数。
结果
ATVr 增加了第 7 天咯萘啶的平均浓度（ATVr 3847.09 ± 893.35ng/ml，对照组 1374.53 ± 265.55ng/ml，p=0.016）和血药浓度-时间曲线下面积（ATVr 670529.57 ± 157172.93ng.h/ml，对照组 447976.28 ± 80886.99ng.h/ml，p=0.224），分别增加了 179.88%和 49.68%，但降低了其平均最大血药浓度（Cmax）（ATVr 13725.70 ± 2658.44ng/ml，对照组 15380.48 ± 2332.62ng/ml，p=0.645），降低了 10.76%。
结论
ATVr 增加了咯萘啶的药物暴露和第 7 天的血药浓度。因此，在服用 ATVr 为基础方案的患者中，AL 被认为是治疗疟疾的有效药物。然而，与这种相互作用相关的安全性仍需要进一步阐明。
试验注册
ClinicalTrials.gov 标识符：NCT04531072，2020 年 8 月 27 日。“回顾性注册”。
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