Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
Antimicrob Agents Chemother. 2012 Apr;56(4):1997-2007. doi: 10.1128/AAC.05756-11. Epub 2012 Jan 17.
Pregnant women are particularly vulnerable to malaria. The pharmacokinetic properties of antimalarial drugs are often affected by pregnancy, resulting in lower drug concentrations and a consequently higher risk of treatment failure. The objective of this study was to evaluate the population pharmacokinetic properties of piperaquine and dihydroartemisinin in pregnant and nonpregnant women with uncomplicated malaria. Twenty-four pregnant and 24 matched nonpregnant women on the Thai-Myanmar boarder were treated with a standard fixed oral 3-day treatment, and venous plasma concentrations of both drugs were measured frequently for pharmacokinetic evaluation. Population pharmacokinetics were evaluated with nonlinear mixed-effects modeling. The main pharmacokinetic finding was an unaltered total exposure to piperaquine but reduced exposure to dihydroartemisinin in pregnant compared to nonpregnant women with uncomplicated malaria. Piperaquine was best described by a three-compartment disposition model with a 45% higher elimination clearance and a 47% increase in relative bioavailability in pregnant women compared with nonpregnant women. The resulting net effect of pregnancy was an unaltered total exposure to piperaquine but a shorter terminal elimination half-life. Dihydroartemisinin was best described by a one-compartment disposition model with a 38% lower relative bioavailability in pregnant women than nonpregnant women. The resulting net effect of pregnancy was a decreased total exposure to dihydroartemisinin. The shorter terminal elimination half-life of piperaquine and lower exposure to dihydroartemisinin will shorten the posttreatment prophylactic effect and might affect cure rates. The clinical impact of these pharmacokinetic findings in pregnant women with uncomplicated malaria needs to be evaluated in larger series.
孕妇特别容易感染疟疾。抗疟药物的药代动力学特性通常会受到妊娠的影响，导致药物浓度降低，治疗失败的风险增加。本研究的目的是评估哌喹和双氢青蒿素在合并疟疾的孕妇和非孕妇中的群体药代动力学特性。在泰缅边境，24 名孕妇和 24 名匹配的非孕妇接受了标准的 3 天固定口服治疗，并经常测量静脉血浆中两种药物的浓度以进行药代动力学评估。采用非线性混合效应模型进行群体药代动力学评估。主要药代动力学发现是，与非孕妇相比，合并疟疾的孕妇的哌喹总暴露量不变，但双氢青蒿素的暴露量减少。哌喹最好用三房室模型来描述，与非孕妇相比，孕妇的消除清除率提高了 45%，相对生物利用度增加了 47%。妊娠的净效应是哌喹的总暴露量不变，但末端消除半衰期缩短。双氢青蒿素最好用单房室模型来描述，与非孕妇相比，孕妇的相对生物利用度降低了 38%。妊娠的净效应是双氢青蒿素的总暴露量减少。哌喹末端消除半衰期缩短和双氢青蒿素暴露量降低将缩短治疗后预防性效果，并可能影响治愈率。这些药代动力学发现对合并疟疾的孕妇的临床影响需要在更大的系列中进行评估。
