Lumefantrine and Desbutyl-Lumefantrine Population Pharmacokinetic-Pharmacodynamic Relationships in Pregnant Women with Uncomplicated Plasmodium falciparum Malaria on the Thailand-Myanmar Border
Lumefantrine and Desbutyl-Lumefantrine Population Pharmacokinetic-Pharmacodynamic Relationships in Pregnant Women with Uncomplicated Plasmodium falciparum Malaria on the Thailand-Myanmar Border
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DOI：
10.1128/aac.00267-15
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发表时间：
2015-10-01
影响因子：
4.9
通讯作者：
Tarning, Joel
中科院分区：
文献类型：
--
作者：
Kloprogge, Frank;McGready, Rose;Tarning, Joel
蒿甲醚-鲁米芬是应用最广泛的以青蒿素为基础的抗疟疾联合治疗。最近的研究表明，第7天的强效代谢物地丁基-鲁米芬三钠的血浆浓度与治疗结果的相关性比鲁米芬三钠更好。据报道，在泰国西北部，使用蒿甲醚-鲁米芬治疗无并发症恶性疟疾的孕妇治愈率较低。基于泰国-缅甸边境116名孕妇的密集静脉和稀疏毛细血管卢布芬和地丁基-卢布芬血浆样本，建立了药物-代谢物同步药代动力学模型。最好的模型被用来评估治疗结果，采用事件发生时间法。在E-max模型中实施的鲁米芬和地丁基-鲁米芬浓度均可预测治疗结果，但鲁米芬提供了更好的预测能力。同时包括鲁米芬和地丁基-鲁米芬的联合模型没有进一步改进该模型。模拟表明，通过延长疗程可以提高恶性疟疾孕妇的治愈率。
Artemether-lumefantrine is the most widely used antimalarial artemisinin-based combination treatment. Recent studies have suggested that day 7 plasma concentrations of the potent metabolite desbutyl-lumefantrine correlate better with treatment outcomes than those of lumefantrine. Low cure rates have been reported in pregnant women with uncomplicated falciparum malaria treated with artemether-lumefantrine in northwest Thailand. A simultaneous pharmacokinetic drug-metabolite model was developed based on dense venous and sparse capillary lumefantrine and desbutyl-lumefantrine plasma samples from 116 pregnant patients on the Thailand-Myanmar border. The best model was used to evaluate therapeutic outcomes with a time-to-event approach. Lumefantrine and desbutyl-lumefantrine concentrations, implemented in an E-max model, both predicted treatment outcomes, but lumefantrine provided better predictive power. A combined model including both lumefantrine and desbutyl-lumefantrine did not improve the model further. Simulations suggested that cure rates in pregnant women with falciparum malaria could be increased by prolonging the treatment course.