Quantifying the pharmacology of antimalarial drug combination therapy.
Quantifying the pharmacology of antimalarial drug combination therapy.
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DOI：
10.1038/srep32762
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发表时间：
2016-09-08
影响因子：
4.6
通讯作者：
Kay K
中科院分区：
文献类型：
--
作者：
Hastings IM;Hodel EM;Kay K
目前大多数抗疟药物是青蒿素与另一类“伙伴”药物的组合，被称为青蒿素联合疗法。它们是治疗人类疟疾感染的一线药物。它们还在公共卫生方面发挥作用，是近期全面扩大疟疾干预和遏制工作的重要组成部分，这些工作被视为长期消除疟疾工作的一部分。最近关于青蒿素产生抗药性的报告引起了相当大的关注。我们通过量化青蒿素对青蒿素综合疗法整体治疗能力的贡献，调查青蒿素耐药性的可能影响。我们实现这一目标，使用一个简单的，容易理解的，代数方法和更复杂的药物作用的药代动力学/药效学分析，这两种方法得到了一致的结果。令人惊讶的是，青蒿素成分通常对最广泛使用的青蒿素综合疗法的治疗能力的贡献可以忽略不计（约0.0001%），只有在对伙伴药物的耐药性开始演变时，青蒿素成分才开始对治疗结果作出重大贡献。对抗疟药物有效性和控制的主要威胁来自对伙伴药物的耐药性。因此，我们认为，公共卫生政策应重新调整，以最大限度地提高合作药物的长期有效性。
Most current antimalarial drugs are combinations of an artemisinin plus a ‘partner’ drug from another class, and are known as artemisinin-based combination therapies (ACTs). They are the frontline drugs in treating human malaria infections. They also have a public-health role as an essential component of recent, comprehensive scale-ups of malaria interventions and containment efforts conceived as part of longer term malaria elimination efforts. Recent reports that resistance has arisen to artemisinins has caused considerable concern. We investigate the likely impact of artemisinin resistance by quantifying the contribution artemisinins make to the overall therapeutic capacity of ACTs. We achieve this using a simple, easily understood, algebraic approach and by more sophisticated pharmacokinetic/pharmacodynamic analyses of drug action; the two approaches gave consistent results. Surprisingly, the artemisinin component typically makes a negligible contribution (≪0.0001%) to the therapeutic capacity of the most widely used ACTs and only starts to make a significant contribution to therapeutic outcome once resistance has started to evolve to the partner drugs. The main threat to antimalarial drug effectiveness and control comes from resistance evolving to the partner drugs. We therefore argue that public health policies be re-focussed to maximise the likely long-term effectiveness of the partner drugs.
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影响因子：
4.3
作者：
Johnston GL;Gething PW;Hay SI;Smith DL;Fidock DA
通讯作者：
Fidock DA
柬埔寨恶性疟原虫疟疾中的双氢青蒿素-哌喹抗药性：一项多地点前瞻性队列研究。
DOI：
10.1016/s1473-3099(15)00487-9
发表时间：
2016-03
期刊：
The Lancet. Infectious diseases
影响因子：
--
作者：
Amaratunga C;Lim P;Suon S;Sreng S;Mao S;Sopha C;Sam B;Dek D;Try V;Amato R;Blessborn D;Song L;Tullo GS;Fay MP;Anderson JM;Tarning J;Fairhurst RM
通讯作者：
Fairhurst RM
影响因子：
3
作者：
Hastings IM;Hodel EM
通讯作者：
Hodel EM
影响因子：
3
作者：
Hodel EM;Kay K;Hayes DJ;Terlouw DJ;Hastings IM
通讯作者：
Hastings IM
DOI：
10.4269/ajtmh.2012.12-0025
发表时间：
2012-08
期刊：
The American journal of tropical medicine and hygiene
影响因子：
--
作者：
Fairhurst RM;Nayyar GML;Breman JG;Hallett R;Vennerstrom JL;Duong S;Ringwald P;Wellems TE;Plowe CV;Dondorp AM
通讯作者：
Dondorp AM