Optimizing the programmatic deployment of the anti-malarials artemether-lumefantrine and dihydroartemisinin-piperaquine using pharmacological modelling.
Optimizing the programmatic deployment of the anti-malarials artemether-lumefantrine and dihydroartemisinin-piperaquine using pharmacological modelling.
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DOI：
10.1186/1475-2875-13-138
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发表时间：
2014-04-07
期刊：
影响因子：
3
通讯作者：
Hastings IM
中科院分区：
文献类型：
--
作者：
Hodel EM;Kay K;Hayes DJ;Terlouw DJ;Hastings IM
抗疟疾药物的成功规划使用面临着标准药物开发过程所不涵盖的挑战。为低资源环境或基于社区的使用制定适当的实用剂量方案没有得到正式监管，尽管这些可能会改变可能会严重影响个体患者和群体水平结果的因素，例如药物暴露、患者依从性和耐药性传播，并可能影响药物的声誉及其最终治疗寿命。抗疟疾药物治疗的计算机药理学模型及蒿甲醚-本芴醇的药代动力学/药效学特征（AM-LF，Coartem®）和双氢青蒿素-哌喹（DHA-PPQ，Eurartesim®），以评估方案因素的潜在影响，包括区域优化的、基于年龄的给药方案、患者依从性差、食物影响和耐药性对人群水平治疗结果的影响，并比较了两种药物对这些因素的敏感性。与DHA-PPQ相比，AM-LF的治疗有效性似乎对影响药物暴露的因素更稳健，例如基于年龄而不是基于体重的给药或依从性差。该模型强调了DHA：PPQ的次优低比例，再加上PPQ相对于DHA的治疗剂量范围较窄，导致体重或年龄临界值，使DHA处于剂量不足的高风险中。对现实生活中的情况进行药理学建模可以提供宝贵的支持性数据，并突出治疗效果的可改变的决定因素，这有助于在控制方案中优化抗疟疾药物的部署。
Successful programmatic use of anti-malarials faces challenges that are not covered by standard drug development processes. The development of appropriate pragmatic dosing regimens for low-resource settings or community-based use is not formally regulated, even though these may alter factors which can substantially affect individual patient and population level outcome, such as drug exposure, patient adherence and the spread of drug resistance and can affect a drug’s reputation and its eventual therapeutic lifespan. An in silico pharmacological model of anti-malarial drug treatment with the pharmacokinetic/pharmacodynamic profiles of artemether-lumefantrine (AM-LF, Coartem®) and dihydroartemisinin-piperaquine (DHA-PPQ, Eurartesim®) was constructed to assess the potential impact of programmatic factors, including regionally optimized, age-based dosing regimens, poor patient adherence, food effects and drug resistance on treatment outcome at population level, and compared both drugs’ susceptibility to these factors. Compared with DHA-PPQ, therapeutic effectiveness of AM-LF seems more robust to factors affecting drug exposure, such as age- instead of weight-based dosing or poor adherence. The model highlights the sub-optimally low ratio of DHA:PPQ which, in combination with the narrow therapeutic dose range of PPQ compared to DHA that drives the weight or age cut-offs, leaves DHA at a high risk of under-dosing. Pharmacological modelling of real-life scenarios can provide valuable supportive data and highlight modifiable determinants of therapeutic effectiveness that can help optimize the deployment of anti-malarials in control programmes.
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影响因子：
3.3
作者：
Depoortere, E;Guthmann, JP;Legros, D
通讯作者：
Legros, D
DOI：
10.1371/journal.pctr.0020020
发表时间：
2007-05-18
期刊：
PLoS clinical trials
影响因子：
--
作者：
Kamya, Moses R;Yeka, Adoke;Dorsey, Grant
通讯作者：
Dorsey, Grant
DOI：
10.4269/ajtmh.2002.66.293
发表时间：
2002-03-01
影响因子：
3.3
作者：
Bindschedler, M;Lefèvre, G;Sioufi, A
通讯作者：
Sioufi, A
影响因子：
15.8
作者：
Achan, Jane;Adam, Ishag;Zongo, Issaka
通讯作者：
Zongo, Issaka
影响因子：
15.8
作者：
Alonso PL;Brown G;Arevalo-Herrera M;Binka F;Chitnis C;Collins F;Doumbo OK;Greenwood B;Hall BF;Levine MM;Mendis K;Newman RD;Plowe CV;Rodríguez MH;Sinden R;Slutsker L;Tanner M
通讯作者：
Tanner M