哌喹在恶性疟疾中的群体药代动力学特性:个体参与者数据荟萃分析。
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Hoglund RM, Workman L, Edstein MD, Thanh NX, Quang NN, Zongo I, Ouedraogo JB, Borrmann S, Mwai L, Nsanzabana C, Price RN, Dahal P, Sambol NC, Parikh S, Nosten F, Ashley EA, Phyo AP, Lwin KM, McGready R, Day NP, Guerin PJ, White NJ, Barnes KI, Tarning J
哌喹在恶性疟疾中的群体药代动力学特性:个体参与者数据荟萃分析。
科学通报，2017;14(1):e1002212。doi: 10.1371 / journal.pmed.1002212。2017年1月
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28072872 (PubMed视图］
- 摘要
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背景:以青蒿素为基础的联合疗法(ACTs)是目前治疗单纯恶性疟原虫疟疾的主要方法，但青蒿素耐药性正在东南亚蔓延。双氢青蒿素-哌喹是世界卫生组织目前推荐的五种以青蒿素为基础的联合疗法之一。以前的研究表明，患有疟疾的幼儿(5岁以下)剂量不足。本研究利用基于人群的药代动力学方法来优化哌喹的抗疟疾治疗方案。方法和发现:通过对1960年1月1日至2013年2月15日发表的文章进行系统文献综述，确定了哌喹的药代动力学研究。来自11项临床研究(来自728人的8,776份样本)的成人和儿童无并发症疟疾患者以及健康志愿者的个体血浆哌喹浓度-时间数据由世界抗疟药网络整理和标准化。使用非线性混合效应模型对数据进行汇总和分析。哌喹的药代动力学成功地描述了具有柔性吸收的三室处置模型。体重显著影响清除率和体积参数，在给予制造商目前推荐的剂量方案后，与较大的儿童和成人(>/=25 kg)相比，幼儿(<25 kg)的哌喹暴露量较低。在推荐的剂量方案下，儿童第7天的模拟中位(四分位数范围)血浆浓度为29.4 (19.3-44.3)ng/ml，而较大的儿童和成人为38.1 (25.8-56.3)ng/ml。 The final model identified a mean (95% confidence interval) increase of 23.7% (15.8%-32.5%) in piperaquine bioavailability between each piperaquine dose occasion. The model also described an enzyme maturation function in very young children, resulting in 50% maturation at 0.575 (0.413-0.711) y of age. An evidence-based optimised dose regimen was constructed that would provide piperaquine exposures across all ages comparable to the exposure currently seen in a typical adult with standard treatment, without exceeding the concentration range observed with the manufacturers' recommended regimen. Limited data were available in infants and pregnant women with malaria as well as in healthy individuals. CONCLUSIONS: The derived population pharmacokinetic model was used to develop a revised dose regimen of dihydroartemisinin-piperaquine that is expected to provide equivalent piperaquine exposures safely in all patients, including in small children with malaria. Use of this dose regimen is expected to prolong the useful therapeutic life of dihydroartemisinin-piperaquine by increasing cure rates and thereby slowing resistance development. This work was part of the evidence that informed the World Health Organization technical guidelines development group in the development of the recently published treatment guidelines (2015).
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