群体药代动力学性质的哌喹恶性疟疾:个体参与者数据荟萃分析。

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霍格伦德RM,工人L, Edstein医学博士Thanh NX, Quang NN,松,韦德JB, Borrmann年代,姆瓦伊•L, Nsanzabana C,价格RN,达P, Sambol数控,帕里克说,Nosten F,阿什利EA, Phyo美联社,伦公里,McGready R,天NP, Guerin PJ,白色的新泽西,巴恩斯KI,冰斗湖J

群体药代动力学性质的哌喹恶性疟疾:个体参与者数据荟萃分析。

科学硕士。2017年1月10,14 (1):e1002212。doi: 10.1371 / journal.pmed.1002212。eCollection 2017年1月。

PubMed ID

28072872 (在PubMed

]

文摘

背景:以青蒿素为基础的联合疗法(ACTs)是当前的主流治疗无并发症恶性疟原虫疟疾,但行动的阻力是东南亚蔓延。Dihydroartemisinin-piperaquine是世界卫生组织目前建议的五幕。先前的研究表明,儿童(< 5 y)与疟疾under-dosed。本研究利用基于人群的药代动力学的方法来优化哌喹抗疟治疗方案。方法和结果:发表的药代动力学研究哌喹被确定通过系统的文献综述的文章发表在1960年1月1日和2013年2月15日之间。从11个人等离子哌喹浓度时间数据的临床研究(8776 728人的样本)与简单的疟疾和成人和儿童健康志愿者整理和标准化的全球抗疟电阻网络。数据汇集和分析了使用非线性mixed-effects造型。three-compartment哌喹药物动力学描述成功的处理模型和灵活的吸收。体重明显间隙和体积参数的影响,导致哌喹曝光小孩低(< 25公斤)相比,较大的儿童和成人后(> / = 25公斤)政府目前制造商的推荐剂量方案。模拟中位数(四分位距)第七天血浆浓度为29.4(19.3 - -44.3)相比,小孩38.1 ng / ml (25.8 - -56.3) ng / ml在较大的儿童和成人,推荐剂量方案。 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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药物

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