Jin Jie, Cao Jie, Zhang Ruoying, Zheng Lifang, Cai Xinjun, Li Jinmeng
Department of Pharmacy, Zhejiang Hospital of Integrated Traditional Chinese and Western Medicine, Hangzhou, 310000, Zhejiang, China.
Eur J Clin Pharmacol. 2025 Mar;81(3):347-363. doi: 10.1007/s00228-024-03788-1. Epub 2025 Jan 8.
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.
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.
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.
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.
贝达喹啉(BDQ)在耐多药结核病(MDR-TB)治疗中发挥着关键作用。然而,BDQ较大的药代动力学(PK)变异性给其临床应用带来了重大挑战。本研究旨在总结BDQ的群体PK特征,并确定影响BDQ PK变异的显著协变量。
对PubMed和Web of Science数据库从建库至2023年10月1日进行系统检索。在本综述中检索并确定了关于BDQ的群体药代动力学(PPK)研究。系统总结了纳入研究的PK特征和显著协变量。
本综述纳入了8项在成人中开展的研究以及1项在儿童和青少年中开展的研究。三室动态吸收转运室模型是BDQ常用的结构模型。体重、种族、白蛋白和合并用药是影响BDQ PK变异的显著协变量。随着体重和白蛋白水平的增加,BDQ的清除率(CL)逐渐升高。儿童每千克体重的平均CL值比成人高1.49倍。黑人种族患者的CL比其他人群高84%。此外,与利福平及利福喷丁合用时,BDQ的清除率分别高出378%和296%。
体重、种族、白蛋白水平和合并用药可能是影响患者暴露差异的重要因素。需要进一步开展BDQ的PPK研究以促进优化给药方案。