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首页> 外文期刊>Antimicrobial agents and chemotherapy. >Pharmacokinetics of dihydroartemisinin and piperaquine in pregnant and nonpregnant women with uncomplicated falciparum malaria.
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Pharmacokinetics of dihydroartemisinin and piperaquine in pregnant and nonpregnant women with uncomplicated falciparum malaria.

机译：双氢青蒿素和哌喹在未发生复杂恶性疟疾的孕妇和非孕妇中的药代动力学。

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Dihydroartemisinin-piperaquine is a fixed-dose artemisinin-based combination treatment. Some antimalarials have altered pharmacokinetics in pregnancy. Pregnant women in the 2nd or 3rd trimester and matched nonpregnant women with uncomplicated falciparum malaria were treated with a total of 6.4 mg/kg of body weight dihydroartemisinin and 51.2 mg/kg piperaquine once daily for 3 days. Venous blood samples were drawn at prespecified time points over 9 weeks. Plasma dihydroartemisinin and piperaquine concentrations were analyzed by liquid chromatography-mass spectrometry. Piperaquine and dihydroartemisinin pharmacokinetics were well described. There were no significant differences in total piperaquine exposure (P = 0.80) or drug exposure during the terminal elimination phase (72 h to infinity) (P = 0.64) between the two groups. The apparent volume of distribution of piperaquine was significantly smaller (602 liters/kg versus 877 liters/kg) in pregnant women than in nonpregnant women (P = 0.0057), and the terminal elimination half-life was significantly shorter (17.8 days versus 25.6 days; P = 0.0023). Dihydroartemisinin exposure after the first dose was significantly lower (844 h x ng/ml versus 1,220 h x ng/ml, P = 0.0021) in pregnant women, but there were no significant differences in total dihydroartemisinin exposure or maximum concentrations between the two groups. There were no significant differences in any pharmacokinetic parameters between the second and third trimester. These results obtained through noncompartmental analysis suggest that in the treatment of falciparum malaria, there are no clinically important differences in the pharmacokinetics of dihydroartemisinin or piperaquine between pregnant and nonpregnant women. However, a more detailed analysis using population pharmacokinetic modeling is needed to fully investigate the differences found for some of the pharmacokinetic parameters, such as the terminal half-life.
机译：双氢青蒿素-哌喹是基于固定剂量青蒿素的联合治疗。一些抗疟药改变了孕妇的药代动力学。妊娠2或3个月的孕妇和配对的未合并恶性疟疾的未怀孕妇女每天接受一次6.4 mg / kg体重的双氢青蒿素和51.2 mg / kg哌喹的治疗，连续3天。在9周的预定时间点抽取静脉血样本。用液相色谱-质谱法分析血浆双氢青蒿素和哌喹浓度。哌喹和二氢青蒿素的药代动力学已有很好的描述。两组在终末消除阶段（从72小时到无限远）（P = 0.64）之间的总哌喹暴露（P = 0.80）或药物暴露无显着差异。孕妇的哌喹喹的表观分布量显着小于未怀孕妇女（602升/公斤，而不是877升/公斤）（P = 0.0057），并且终末消除半衰期显着缩短（17.8天比25.6天）。 ; P = 0.0023）。孕妇初次注射双氢青蒿素的剂量显着降低（844 h x ng / ml与1,220 h x ng / ml，P = 0.0021），但两组间双氢青蒿素的总暴露量或最高浓度无显着差异。在妊娠中期和中期，任何药代动力学参数均无显着差异。通过非房室分析获得的这些结果表明，在恶性疟疾的治疗中，孕妇和非孕妇中双氢青蒿素或哌喹的药代动力学在临床上没有重要差异。但是，需要使用群体药代动力学模型进行更详细的分析，以全面研究某些药代动力学参数（例如最终半衰期）的差异。

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