坦桑尼亚姆万扎未合并恶性疟原虫感染的间日疟患者采用青蒿琥酯-咯萘啶治疗时的无控制条件下的咯萘啶血药浓度。

Lumefantrine plasma concentrations in uncontrolled conditions among patients treated with artemether-lumefantrine for uncomplicated plasmodium falciparum malaria in Mwanza, Tanzania.

机构信息

Department of Pharmacology, Catholic University of Health and Allied Sciences, Mwanza, Tanzania.

出版信息

Int J Infect Dis. 2022 Oct;123:192-199. doi: 10.1016/j.ijid.2022.08.020. Epub 2022 Sep 5.

DOI:10.1016/j.ijid.2022.08.020

PMID:36064162

Abstract

BACKGROUND

Therapeutic efficacy of artemether-lumefantrine is highly dependent on adequate systemic exposure to the partner drug lumefantrine particularly day 7 lumefantrine plasma concentration. There has been contradicting findings on the role of the cut-off values in predicting treatment outcomes among malaria patients in malaria endemic regions. This study assesses the day 3 and 7 lumefantrine plasma concentrations including related determinant factors and their influence on treatment outcomes among treated Tanzanian children and adults in uncontrolled conditions (real life condition).

METHODS

Data was nested from an efficacy study employing the WHO protocol, 2015 for monitoring antimalarial drug efficacy. Lumefantrine plasma concentration was measured by high performance liquid chromatography with ultraviolet (HPLC-UV).

RESULTS

Lumefantrine plasma concentrations below 175ng/ml and 200ng/ml on day 3 and 7 did not affect adequate clinical and parasitological response (ACPR) and recurrence of infection (p = 0.428 and 0.239 respectively). Age and baseline parasitemia were not associated to day 3 median lumefantrine plasma concentrations (p = 0.08 and 0.31 respectively) and day 7 lumefantrine plasma concentrations (p = 0.07 and 0.41 respectively). However, the day 3 and day 7 lumefantrine plasma concentrations were significantly higher in males compared to females (p = 0.03 and 0.042 respectively).

CONCLUSION

Lumefantrine plasma concentrations below cut-off points (175ng/ml and 200ng/ml) on day 3 and 7 did not influence treatment outcomes.

摘要

背景

青蒿琥酯-咯萘啶的治疗效果高度依赖于药物母体咯萘啶在体内的充分暴露，尤其是第 7 天的咯萘啶血药浓度。在疟疾流行地区，关于这些切点值在预测疟疾患者治疗结局中的作用，存在相互矛盾的研究结果。本研究评估了在未控制条件（真实生活条件）下，青蒿琥酯-咯萘啶治疗的坦桑尼亚儿童和成人的第 3 天和第 7 天的咯萘啶血药浓度及其相关决定因素，以及它们对治疗结局的影响。

方法

该数据是嵌套于一项 2015 年采用世界卫生组织（WHO）方案进行的抗疟药物疗效监测的疗效研究中。咯萘啶血药浓度采用高效液相色谱法-紫外检测（HPLC-UV）进行测定。

结果

第 3 天和第 7 天的咯萘啶血药浓度低于 175ng/ml 和 200ng/ml 并不会影响充分的临床和寄生虫学应答（ACPR）和感染复发（p 值分别为 0.428 和 0.239）。年龄和基线疟原虫密度与第 3 天的咯萘啶血药浓度中位数（p 值分别为 0.08 和 0.31）和第 7 天的咯萘啶血药浓度（p 值分别为 0.07 和 0.41）无关。然而，第 3 天和第 7 天的男性咯萘啶血药浓度明显高于女性（p 值分别为 0.03 和 0.042）。