Department of Clinical Pharmacology, ICMR-National Institute for Research in Tuberculosis, No.1 Mayor Sathiyamoorthy Road, Chetpet, Chennai 600 031, Tamil Nadu, India.
Pediatric Infectious Diseases and Pediatric GI, Hepatology, Pediatric DR TB (State), Center of Excellence, Department of Pediatric Infectious Diseases, B.J. Wadia Hospital for Children, Mumbai, India.
J Antimicrob Chemother. 2024 Nov 4;79(11):2939-2947. doi: 10.1093/jac/dkae311.
Drug-resistant tuberculosis (DR-TB) is one of the challenging forms of TB to treat, not only in adults but also in children and adolescents. Further, there is a void in the treatment strategy exclusively for children due to various reasons, including paucity of pharmacokinetic (PK) data on anti-TB drugs across the globe. In this context, the present study aimed at assessing the PK of some of the anti-TB drugs used in DR-TB treatment regimens.
A multicentre observational study was conducted among DR-TB children and adolescents (n = 200) aged 1-18 years (median: 12 years; IQR: 9-14) treated under programmatic settings in India. Steady-state PK (intensive: n = 89; and sparse: n = 111) evaluation of moxifloxacin, levofloxacin, cycloserine, ethionamide, rifampicin, isoniazid and pyrazinamide was carried out by measuring plasma levels using HPLC methods.
In the study population, the frequency of achieving peak plasma concentrations ranged between 13% (for rifampicin) to 82% (for pyrazinamide), whereas the frequency of suboptimal peak concentration for pyrazinamide, cycloserine, moxifloxacin, levofloxacin and rifampicin was 15%, 19%, 29%, 41% and 74%, respectively. Further, the frequency of supratherapeutic levels among patients varied between 3% for pyrazinamide and 60% for isoniazid. In the below-12 years age category, the median plasma maximum concentration and 12 h exposure of moxifloxacin were significantly lower than that of the above-12 years category despite similar weight-adjusted dosing.
Age significantly impacted the plasma concentration and exposure of moxifloxacin. The observed frequencies of suboptimal and supratherapeutic concentrations underscore the necessity for dose optimization and therapeutic drug monitoring in children and adolescents undergoing DR-TB treatment.
耐药结核病（DR-TB）不仅在成人中，而且在儿童和青少年中都是一种难以治疗的结核病形式。此外，由于全球范围内抗结核药物药代动力学（PK）数据不足等各种原因，专门针对儿童的治疗策略存在空白。在这种情况下，本研究旨在评估用于 DR-TB 治疗方案的一些抗结核药物的 PK。
在印度的规划环境中，对 1-18 岁（中位数：12 岁；IQR：9-14 岁）的 DR-TB 儿童和青少年（n=200）进行了一项多中心观察性研究。使用 HPLC 方法测量血浆水平，对莫西沙星、左氧氟沙星、环丝氨酸、乙胺丁醇、利福平、异烟肼和吡嗪酰胺进行了密集型（n=89）和稀疏型（n=111）稳态 PK 评估。
在研究人群中，达到峰值血浆浓度的频率范围在 13%（利福平）至 82%（吡嗪酰胺）之间，而吡嗪酰胺、环丝氨酸、莫西沙星、左氧氟沙星和利福平的亚最佳峰值浓度频率分别为 15%、19%、29%、41%和 74%。此外，患者中存在治疗性药物监测的频率在 3%（吡嗪酰胺）至 60%（异烟肼）之间有所不同。在 12 岁以下年龄组中，尽管进行了相似的体重调整剂量，但莫西沙星的中位血浆最大浓度和 12 小时暴露量明显低于 12 岁以上年龄组。
年龄显著影响莫西沙星的血浆浓度和暴露量。观察到的亚最佳和治疗性药物监测频率表明，在接受 DR-TB 治疗的儿童和青少年中，需要进行剂量优化和治疗性药物监测。
