Population pharmacokinetics of bedaquiline: a systematic review.

IF 2.4 3区医学 Q3 PHARMACOLOGY & PHARMACY

European Journal of Clinical Pharmacology Pub Date : 2025-01-08 DOI:10.1007/s00228-024-03788-1

Jie Jin, Jie Cao, Ruoying Zhang, Lifang Zheng, Xinjun Cai, Jinmeng Li

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引用次数: 0

Abstract

Background and objectives: Bedaquiline (BDQ) plays a critical role in the treatment of multidrug-resistant tuberculosis (MDR-TB). However, the large pharmacokinetic (PK) variability of BDQ presents a significant challenge in its clinical use. This study aimed to summarize the population PK characteristics of BDQ and to identify significant covariates affecting the PK variation of BDQ.

Methods: The PubMed and Web of Science databases were systematically searched from their inception to October 1, 2023. Population pharmacokinetics (PPK) studies on BDQ were searched and identified in this review. The PK characteristics of included studies and the significant covariates were systematically summarized.

Results: Eight studies conducted in adults and one in children and adolescents were included in this review. A three disposition compartments with dynamic absorption transport chamber model was the commonly used structural model for BDQ. Body weight, race, albumin, and concomitant medication were significant covariates affecting BDQ PK variation. With the increase of weight and albumin levels, the clearance (CL) of BDQ was gradually increased. The average CL value per body weight in children was 1.49-fold higher than that in adults. Black race patients had an 84% higher CL than other populations. Moreover, combined with rifampicin and rifapentine, BDQ had 378% and 296% higher clearance rates, respectively.

Conclusions: Body weight, race, albumin level, and concomitant medication may be important factors affecting patients' exposure differences. Further PPK studies of BDQ are needed to facilitate optimal dosing regimens.

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贝达喹啉的群体药代动力学：系统综述。

背景与目的：贝达喹啉（BDQ）在耐多药结核病（MDR-TB）的治疗中发挥着关键作用。然而，BDQ的大药代动力学（PK）变异性对其临床应用提出了重大挑战。本研究的目的是总结BDQ种群PK特征，找出影响BDQ PK变化的显著协变量。方法：系统检索PubMed和Web of Science数据库，检索时间从建站到2023年10月1日。本综述检索并确定了BDQ的群体药代动力学（PPK）研究。系统总结纳入研究的PK特性及显著协变量。结果：本综述纳入了8项成人研究和1项儿童和青少年研究。三配置室动态吸收输运室模型是BDQ常用的结构模型。体重、种族、白蛋白和伴随用药是影响BDQ PK变化的重要协变量。随着体重和白蛋白水平的增加，BDQ清除率（CL）逐渐升高。儿童每体重的平均CL值是成人的1.49倍。黑人患者的CL比其他人群高84%。BDQ与利福平、利福喷丁联合使用，清除率分别提高378%和296%。结论：体重、种族、白蛋白水平及伴随用药可能是影响患者暴露差异的重要因素。需要对BDQ进行进一步的PPK研究，以促进最佳给药方案。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

European Journal of Clinical Pharmacology 医学-药学

CiteScore

5.40

自引率

3.40%

发文量

170

审稿时长

3-8 weeks

期刊介绍： The European Journal of Clinical Pharmacology publishes original papers on all aspects of clinical pharmacology and drug therapy in humans. Manuscripts are welcomed on the following topics: therapeutic trials, pharmacokinetics/pharmacodynamics, pharmacogenetics, drug metabolism, adverse drug reactions, drug interactions, all aspects of drug development, development relating to teaching in clinical pharmacology, pharmacoepidemiology, and matters relating to the rational prescribing and safe use of drugs. Methodological contributions relevant to these topics are also welcomed. Data from animal experiments are accepted only in the context of original data in man reported in the same paper. EJCP will only consider manuscripts describing the frequency of allelic variants in different populations if this information is linked to functional data or new interesting variants. Highly relevant differences in frequency with a major impact in drug therapy for the respective population may be submitted as a letter to the editor. Straightforward phase I pharmacokinetic or pharmacodynamic studies as parts of new drug development will only be considered for publication if the paper involves -a compound that is interesting and new in some basic or fundamental way, or -methods that are original in some basic sense, or -a highly unexpected outcome, or -conclusions that are scientifically novel in some basic or fundamental sense.