Supervised versus unsupervised antimalarial treatment with six-dose artemether-lumefantrine: pharmacokinetic and dosage-related findings from a clinical trial in Uganda
Supervised versus unsupervised antimalarial treatment with six-dose artemether-lumefantrine: pharmacokinetic and dosage-related findings from a clinical trial in Uganda
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DOI：
10.1186/1475-2875-5-59
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发表时间：
2006-07-19
期刊：
影响因子：
3
通讯作者：
Guthmann, Jean-Paul
中科院分区：
文献类型：
--
作者：
Checchi, Francesco;Piola, Patrice;Guthmann, Jean-Paul
工作背景：蒿甲醚-苯芴醇（A/L）的六剂抗疟疗法可能很快成为非洲最广泛使用的药物组合之一，尽管由于营养不足以及缺乏药代动力学和有效性数据，在坚持和吸收不良方面可能存在限制。在乌干达恶性疟原虫稳定传播环境中进行的监督与非监督A/L治疗试验中，在入选后第3天（C [lum]（第3天））和第7天（C [lum]（第7天））测量一组患者的血浆本芴醇浓度。本芴醇浓度的预测因素进行了分析，以显示C [lum]（第7天）和体重调整的本芴醇剂量如何影响28天复发和再感染风险。这些新的发现的影响进行了讨论，在出现的苯芴醇耐药菌株在Africa.Results：C [LUM]（第3天）和C [LUM]（第7天）之间的分布241监督和238无监督的患者正偏。无监督治疗和降低体重调整的本芴醇剂量与C [lum]（第3天）呈负相关。无监督治疗和年龄下降与C [ lum]第7天呈强负相关。两种模型的预测性都很差（R平方
Background: A six-dose antimalarial regimen of artemether-lumefantrine (A/L) may soon become one of the most widely used drug combination in Africa, despite possible constraints with adherence and poor absorption due to inadequate nutrition, and a lack of pharmacokinetic and effectiveness data.Methods: Within a trial of supervised versus unsupervised A/L treatment in a stable Ugandan Plasmodium falciparum transmission setting, plasma lumefantrine concentrations were measured in a subset of patients on day 3 (C [lum](day3)) and day 7 (C [lum](day7)) post-inclusion. Predictors of lumefantrine concentrations were analysed to show how both C [lum](day7) and the weight-adjusted lumefantrine dose affect 28-day recrudescence and re-infection risks. The implications of these novel findings are discussed in terms of the emergence of lumefantrine-resistant strains in Africa.Results: C [lum](day3) and C [lum](day7) distributions among 241 supervised and 238 unsupervised patients were positively skewed. Unsupervised treatment and decreasing weight-adjusted lumefantrine dose were negatively associated with C [lum](day3). Unsupervised treatment and decreasing age showed strong negative associations with C [ lum] day7. Both models were poorly predictive (R-squared