A systematic review on the effect of diabetes mellitus on the pharmacokinetics of TB drugs.

IF 3.4 3区医学 Q2 INFECTIOUS DISEASES

International Journal of Tuberculosis and Lung Disease Pub Date : 2024-09-01 DOI:10.5588/ijtld.23.0507

M Cevik, A Sturdy, A E Maraolo, B G J Dekkers, O W Akkerman, S H Gillespie, J W C Alffenaar

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Abstract

OBJECTIVESThe coexistence of TB and diabetes mellitus (DM) (TB-DM) is associated with an increased risk of treatment failure, death, delayed culture conversion, and drug resistance. Because plasma concentrations may influence clinical outcomes, we evaluated the evidence on the pharmacokinetic (PK) of TB drugs in individuals with DM to guide management.METHODSWe performed a systematic review and meta-analysis through searches of major databases from 1946 to 6 July 2023. PROSPERO (CRD42022323566).RESULTSOf 4,173 potentially relevant articles, we identified 16 studies assessing rifampicin (RIF) PK, 9 on isoniazid (INH), 8 on pyrazinamide (PZA), and 3 on ethambutol (EMB). Two studies reported on second-line anti-TB drugs. According to our meta-analysis, RIF time to maximum concentration (T_max) was significantly prolonged in patients with DM compared with non-DM patients. We found no significant differences for RIF C_max, area under the curve (AUC) 0-24 or drug concentration at 2 h (C2h), INH C2h, PZA C2h, PZA T_max, and EMB T_max. Although RIF C2h was slightly reduced in patients with TB-DM, this finding was not statistically significant.CONCLUSIONSThis review comprehensively examines the impact of DM on the PK of TB drugs. We observed significant heterogeneity among the studies. Given the association between lower plasma concentrations and poor clinical outcomes among patients with DM, we recommend a higher dose limit to compensate for the larger body weight of patients with DM..

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糖尿病对结核病药物代谢动力学影响的系统回顾。

目的结核病和糖尿病（DM）并存（TB-DM）与治疗失败、死亡、培养转换延迟和耐药性风险增加有关。由于血浆浓度可能会影响临床结果，因此我们评估了结核病药物在糖尿病患者体内的药代动力学（PK）证据，以指导治疗。方法我们通过检索 1946 年至 2023 年 7 月 6 日期间的主要数据库，进行了系统综述和荟萃分析。结果在 4,173 篇可能相关的文章中，我们发现了 16 篇评估利福平 (RIF) PK 的研究、9 篇评估异烟肼 (INH) PK 的研究、8 篇评估吡嗪酰胺 (PZA) PK 的研究和 3 篇评估乙胺丁醇 (EMB) PK 的研究。两项研究报告了二线抗结核药物。根据我们的荟萃分析，与非 DM 患者相比，DM 患者 RIF 达到最大浓度（Tmax）的时间明显延长。我们发现 RIF Cmax、0-24 小时曲线下面积（AUC）或 2 小时药物浓度（C2h）、INH C2h、PZA C2h、PZA Tmax 和 EMB Tmax 均无明显差异。虽然 RIF C2h 在 TB-DM 患者中略有降低，但这一结果并无统计学意义。我们观察到研究之间存在明显的异质性。鉴于 DM 患者较低的血浆浓度与较差的临床结果之间存在关联，我们建议采用较高的剂量限制，以补偿 DM 患者较大的体重。

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

International Journal of Tuberculosis and Lung Disease 医学-传染病学

CiteScore

4.90

自引率

20.00%

发文量

266

审稿时长

2 months

期刊介绍： The International Journal of Tuberculosis and Lung Disease publishes articles on all aspects of lung health, including public health-related issues such as training programmes, cost-benefit analysis, legislation, epidemiology, intervention studies and health systems research. The IJTLD is dedicated to the continuing education of physicians and health personnel and the dissemination of information on tuberculosis and lung health world-wide.