Pharmacokinetic Profile of Artemisinin Derivatives and Companion Drugs Used in Artemisinin-Based Combination Therapies for the Treatment of Plasmodium falciparum Malaria in Children
Pharmacokinetic Profile of Artemisinin Derivatives and Companion Drugs Used in Artemisinin-Based Combination Therapies for the Treatment of Plasmodium falciparum Malaria in Children
复制标题
青蒿素衍生物和用于以青蒿素为基础的联合疗法治疗儿童恶性疟原虫疟疾的伴随药物的药代动力学特征
DOI：
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发表时间：
2013
影响因子：
4.5
通讯作者：
M. H. Ensom
中科院分区：
文献类型：
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作者：
S. Pawluk;K. Wilby;M. H. Ensom
疟疾是全世界最常见的寄生虫感染之一。恶性疟原虫是非洲最流行的菌株，也是最致命的菌株。这种疾病尤其影响儿童，2010 年，5 岁以下儿童约占疟疾死亡人数的 86%。本次综述的目的是总结和评估已发表的文献，这些文献报告了用于治疗儿童恶性疟的青蒿素联合用药的药代动力学参数，并确定和讨论有关这些药物在儿童中的药代动力学的争议。对 MEDLINE（1948 年至 2012 年 9 月）、EMBASE（1980 年至 2012 年 9 月）、国际药物文摘（1970 年至 2012 年 9 月）、Google 和 Google Scholar 进行了搜索，以查找描述儿童抗疟药药代动力学的文章。我们检索了 30 篇文章，其中 23 篇被纳入综述：青蒿素类化合物，12 篇；苯芴醇，四篇文章；阿莫地喹，五篇文章；磺胺多辛，六篇文章；乙胺嘧啶，一篇；甲氟喹，三篇文章；和哌喹，两篇文章。根据比较组和主要发现对研究进行了总结。存在许多争议，包括新剂型的药代动力学等效性、儿童与成人药代动力学参数的改变、药物相互作用的影响以及药代动力学变化与临床结果的关联。许多抗疟药物的药代动力学参数存在很大差异，这可能是每个儿科队列的年龄和/或体重范围广泛的结果。这些研究可能掩盖了与年龄和体重的重要关联，并产生不能充分代表整个儿科人群的平均数据。为了正确评估此类药代动力学变化的临床影响并推荐安全有效的剂量方案，迫切需要对用于恶性疟原虫儿科人群的所有推荐的一线和二线药物以及不同的药物配方进行剂量优化研究。
Malaria is one of the most common parasitic infections worldwide. Plasmodium falciparum is the most prevalent strain in Africa and also the most fatal. The disease especially affects children, with those under age 5 years accounting for approximately 86 % of malaria deaths in 2010. The objectives of this review are to summarize and evaluate published literature reporting the pharmacokinetic parameters of artemisinin-based combinations used to treat P. falciparum in paediatric populations and to identify and discuss controversies regarding pharmacokinetics of these agents in children. A search of MEDLINE (1948–September 2012), EMBASE (1980–September 2012), International Pharmaceutical Abstracts (1970–September 2012), Google and Google Scholar was conducted for articles describing pharmacokinetics of antimalarials in children. Our search produced 30 articles, of which 23 were included in the review: artemisinin compounds, 12 articles; lumefantrine, four articles; amodiaquine, five articles; sulfadoxine, six articles; pyrimethamine, one article; mefloquine, three articles; and piperaquine, two articles. Studies were summarized based on comparison groups and major findings. Many controversies were identified, including pharmacokinetic equivalence of novel dosage forms, altered pharmacokinetic parameters in children versus adults, effect of drug interactions, and association of pharmacokinetic changes with clinical outcomes. A large variation in pharmacokinetic parameters of many antimalarial agents was shown, which may be a consequence of the wide range of ages and/or bodyweights of each paediatric cohort. These studies may mask important associations with age and bodyweight and produce mean data that do not adequately represent the paediatric population as a whole. In order to properly assess the clinical implications of such pharmacokinetic changes and recommend safe and effective dosage regimens, there is an urgent need for dose-optimization studies for all recommended first- and second-line agents, along with the different drug formulations, used in paediatric populations with P. falciparum.