利用药代动力学-药效学模拟优化疟疾肆虐严重国家幼儿的鲁米凡林剂量

IF 3.8 4区 医学 Q2 IMMUNOLOGY
Open Forum Infectious Diseases Pub Date : 2024-10-17 eCollection Date: 2024-11-01 DOI:10.1093/ofid/ofae627
Segolene Simeon, Emma Hughes, Erika Wallender, Belén P Solans, Rada Savic
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引用次数: 0

摘要

背景:蒿甲醚-本芴醇是治疗无并发症疟疾最广泛使用的药物,根据世界卫生组织(WHO)的指导方针,蒿甲醚-本芴醇的剂量以体重带为基础。然而,儿童很容易出现剂量不足的情况。剂量不足会导致治疗失败和耐药性:372 363 名儿童的营养参数:我们估计,在使用世界卫生组织治疗指南时,75%的儿童达到了 200 毫微克/毫升的鲁米芬特林阈值,77%的儿童在 42 天内没有感染疟疾。改用替代给药法后,达到目标卢曼群胺水平的儿童增加了 5%;使用替代给药法和延长疗程达到目标水平的儿童增加了 22%。在联合使用替代给药法和延长给药法的情况下,97%的儿童达到了200纳克/毫升的卢曼芬特林浓度,88%的儿童在42天内没有感染疟疾:这项研究强调了对体重不足的幼儿使用基于体重的鲁米芬特林剂量的不足之处,并支持对营养不良儿童使用基于预期体重的延长剂量进行临床试验的必要性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Optimizing Lumefantrine Dosing for Young Children in High-Malaria-Burden Countries Using Pharmacokinetic-Pharmacodynamic Simulations.

Background: Artemether-lumefantrine is the most widely used treatment for uncomplicated malaria and it is dosed based on weight bands according to World Health Organization (WHO) guidelines. However, children are vulnerable to underdosing. Inadequate dosing can lead to treatment failure and drug resistance.

Methods: Nutritional parameters for 372 363 children <5 years old in 25 high-malaria-burden countries were acquired from the Demographic and Health Surveys program. Prevalence of attaining day 7 lumefantrine concentrations ≥200 ng/mL and remaining reinfection free for 42 days were evaluated using a simulation-based approach with a population pharmacokinetic-pharmacodynamic model. Besides the WHO-recommended lumefantrine dosing regimen (twice daily for 3 days), we explored 3 adjusted regimens: extended (2 extra days of dosing), increased (1 extra 120-mg tablet per dose), and intensified (thrice daily for 3 days). We also explored an alternative method dosing malnourished children based on expected weight for age.

Results: We estimated that 75% of children reached the 200 ng/mL lumefantrine threshold and 77% were malaria free for 42 days when using WHO treatment guidelines. By switching to the alternative dosing method, 5% more children achieved target lumefantrine levels; 22% more achieved the target using the alternative dosing and the extended regimen. With combined alternative plus extended dosing, 97% of children reached 200 ng/mL lumefantrine and 88% were malaria free for 42 days.

Conclusions: This study highlights the inadequacies of weight-based lumefantrine dosing for young and underweight children and supports the need of clinical trials using extended dosing based on expected weight in malnourished children.

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来源期刊
Open Forum Infectious Diseases
Open Forum Infectious Diseases Medicine-Neurology (clinical)
CiteScore
6.70
自引率
4.80%
发文量
630
审稿时长
9 weeks
期刊介绍: Open Forum Infectious Diseases provides a global forum for the publication of clinical, translational, and basic research findings in a fully open access, online journal environment. The journal reflects the broad diversity of the field of infectious diseases, and focuses on the intersection of biomedical science and clinical practice, with a particular emphasis on knowledge that holds the potential to improve patient care in populations around the world. Fully peer-reviewed, OFID supports the international community of infectious diseases experts by providing a venue for articles that further the understanding of all aspects of infectious diseases.
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