Population pharmacokinetics of piperaquine after two different treatment regimens with dihydroartemisinffi-piperaquine in patients with Plasmodium falciparum malaria in Thailand
Population pharmacokinetics of piperaquine after two different treatment regimens with dihydroartemisinffi-piperaquine in patients with Plasmodium falciparum malaria in Thailand
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DOI：
10.1128/aac.00955-07
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发表时间：
2008-03-01
影响因子：
4.9
通讯作者：
White, N. J.
中科院分区：
文献类型：
--
作者：
Tarning, J.;Ashley, E. A.;White, N. J.
对两种不同剂量方案的双氢青蒿素-哌喹治疗的无并发症恶性疟原虫疟疾成人和儿童中哌喹的群体药代动力学进行了表征。在98名3 - 55岁的缅甸和克伦族患者中，阿喹的药代动力学通过双室分布模型进行描述，所有参数均具有一级吸收和个体间随机变异性，并且与三次和四次给药方案相似。儿童的体重标准化口服清除率低于成人，导致终末消除半衰期较长，哌喹总暴露量较高（0 - 63天的浓度-时间曲线下面积[AUC（天）0-63]）。然而，儿童在治疗相关的治疗后预防期（AUC（第3-20天））的血浆浓度较低，因为体重标准化的中心分布容积较小，分布半衰期较短。我们的数据进一步支持简化的每日一次治疗方案，以提高治疗依从性和疗效，并表明儿童中体重调整的哌喹剂量可能需要高于成人。
The population pharmacokinetics of piperaquine in adults and children with uncomplicated Plasmodium falciparum malaria treated with two different dosage regimens of dihydroartemisinin-piperaquine were characterized. Piperaquine pharmacokinetics in 98 Burmese and Karen patients aged 3 to 55 years were described by a two-compartment disposition model with first-order absorption and interindividual random variability on all parameters and were similar with the three- and four-dose regimens. Children had a lower body weight-normalized oral clearance than adults, resulting in longer terminal elimination half-lives and higher total exposure to piperaquine (area under the concentration-time curve from 0 to 63 days [AUC(day) 0-63]). However, children had lower plasma concentrations in the therapeutically relevant posttreatment prophylactic period (AUC(day) 3-20) because of smaller body weight-normalized central volumes of distribution and shorter distribution half-lives. Our data lend further support to a simplified once-daily treatment regimen to improve treatment adherence and efficacy and indicate that weight-adjusted piperaquine doses in children may need to be higher than in adults.