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首页> 外文期刊>Antimicrobial agents and chemotherapy. >Interaction between artemether-lumefantrine and nevirapine-based antiretroviral therapy in HIV-1-infected patients.
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Interaction between artemether-lumefantrine and nevirapine-based antiretroviral therapy in HIV-1-infected patients.

机译：Artemether-lumefantrine与基于奈韦拉平的抗逆转录病毒疗法在HIV-1感染患者之间的相互作用。

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Artemether-lumefantrine and nevirapine-based antiretroviral therapy (ART) are the most commonly recommended first-line treatments for malaria and HIV, respectively, in Africa. Artemether, lumefantrine, and nevirapine are metabolized by the cytochrome P450 3A4 enzyme system, which nevirapine induces, creating potential for important drug interactions. In a parallel-design pharmacokinetic study, concentration-time profiles were obtained in two groups of HIV-infected patients: ART-naive patients and those stable on nevirapine-based therapy. Both groups received the recommended artemether-lumefantrine dose. Patients were admitted for intense pharmacokinetic sampling (0 to 72 h) with outpatient sampling until 21 days. Concentrations of lumefantrine, artemether, dihydroartemisinin, and nevirapine were determined by validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods. The primary outcome was observed day 7 lumefantrine concentrations, as these are associated with therapeutic response in malaria. We enrolled 36 patients (32 females). Median (range) day 7 lumefantrine concentrations were 622 ng/ml (185 to 2,040 ng/ml) and 336 ng/ml (29 to 934 ng/ml) in the nevirapine and ART-naive groups, respectively (P = 0.0002). The median artemether area under the plasma concentration-time curve from 0 to 8 h [AUC((0-8 h))] (P < 0.0001) and dihydroartemisinin AUC((60-68 h)) (P = 0.01) were lower in the nevirapine group. Combined artemether and dihydroartemisinin exposure decreased over time only in the nevirapine group (geometric mean ratio [GMR], 0.76 [95% confidence interval {CI}, 0.65 to 0.90]; P < 0.0001) and increased with the weight-adjusted artemether dose (GMR, 2.12 [95% CI, 1.31 to 3.45]; P = 0.002). Adverse events were similar between groups, with no difference in electrocardiographic Fridericia corrected QT and P-R intervals at the expected time of maximum lumefantrine concentration (T(max)). Nevirapine-based ART decreased artemether and dihydroartemisinin AUCs but unexpectedly increased lumefantrine exposure. The mechanism of the lumefantrine interaction remains to be elucidated. Studies investigating the interaction of nevirapine and artemether-lumefantrine in HIV-infected patients with malaria are urgently needed.
机译：在非洲，蒿甲醚-卢美替林和基于奈韦拉平的抗逆转录病毒疗法（ART）分别是疟疾和艾滋病毒最常用的推荐一线治疗方法。蒿甲醚，lumantantrine和奈韦拉平被奈韦拉平诱导的细胞色素P450 3A4酶系统代谢，为重要的药物相互作用创造了潜力。在一项平行设计的药代动力学研究中，在两组被HIV感染的患者中获得了浓度-时间曲线：未接受ART治疗的患者和接受奈韦拉平治疗的患者。两组均接受了推荐的蒿甲醚-卢美他汀剂量。患者入院接受强力药代动力学采样（0至72小时），门诊采样直至21天。通过已验证的液相色谱-串联质谱法（LC-MS / MS）确定了lumantantrine，蒿甲醚，双氢青蒿素和奈韦拉平的浓度。主要结果是在第7天观察到的红褐素浓度，因为这些浓度与疟疾的治疗反应相关。我们招募了36名患者（32名女性）。奈韦拉平组和未接受过抗病毒治疗的组中，第7天的西酞菁浓度中位数分别为622 ng / ml（185至2,040 ng / ml）和336 ng / ml（29至934 ng / ml）（P = 0.0002）。血浆浓度-时间曲线下从0到8 h [AUC（（0-8 h））]（P <0.0001）和双氢青蒿素AUC（（60-68 h））（P = 0.01）的中位数蒿甲醚面积较低在奈韦拉平组中。仅在奈韦拉平组中，蒿甲醚和双氢青蒿素的联合暴露随时间减少（几何平均比率[GMR]，0.76 [95％置信区间{CI}，0.65至0.90]; P <0.0001），并随着体重调整的蒿甲醚剂量的增加而增加（ GMR，2.12 [95％CI，1.31至3.45]; P ＝ 0.002）。两组之间的不良事件相似，在预期的最大氟尿嘧啶浓度（T（max））时，心电图Fridericia校正的QT和P-R间隔无差异。基于奈韦拉平的抗逆转录病毒药物减少了蒿甲醚和双氢青蒿素的AUCs，但出乎意料的增加了红花青素的暴露。荧光素相互作用的机理还有待阐明。迫切需要进行研究，以研究奈韦拉平和蒿甲醚-卢美他汀在被HIV感染的疟疾患者中的相互作用。

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