Pharmacokinetics-pharmacodynamics of first-line antitubercular drugs: a comparative study in tuberculosis patients with and without concomitant diabetes mellitus

IF 2.4 3区医学 Q3 PHARMACOLOGY & PHARMACY

European Journal of Clinical Pharmacology Pub Date : 2024-09-17 DOI:10.1007/s00228-024-03754-x

Sourav Mondal, Vandana Roy, Girish Gulab Meshram, Ashwani Khanna, Thirumurthy Velpandian, Sandeep Garg

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Abstract

Purpose

To observe the variability in the plasma concentrations and pharmacokinetic-pharmacodynamic (PK-PD) profiles of first-line antitubercular drugs in pulmonary tuberculosis (TB) patients with and without diabetes mellitus (DM).

Methods

Newly diagnosed pulmonary TB patients aged 18–60 years with or without DM were included in the study. Group I (n = 20) included patients with TB, whereas group II (n = 20) included patients with both TB and DM. After 2 weeks of therapy, plasma concentrations and other PK-PD parameters were determined. Improvements in clinical features, X-ray findings, sputum conversion, and adverse drug reactions (ADRs) were assessed after 2 months of therapy.

Results

Isoniazid displayed non-significantly higher plasma concentrations in diabetic patients, along with a significantly (P < 0.05) longer elimination half-life (t_1/2). Rifampicin plasma concentrations at 4, 8, and 12 h were significantly (P < 0.05) lower, and it displayed significantly (P < 0.05) lower area under the curve (AUC_0-12 and AUC_0-∞), shorter t_1/2, higher clearance (Cl), and a lower AUC_0-∞/MIC ratio in diabetic patients. Pyrazinamide and ethambutol showed non-significantly higher plasma concentrations, AUC_0-12, AUC_0-∞, and t_1/2 in diabetic patients. The improvements in clinical features, X-ray findings, sputum conversion, and ADRs were comparable in both groups.

Conclusions

The presence of DM in TB patients affects the PK-PD parameters of isoniazid, rifampicin, pyrazinamide, and ethambutol variably in the Indian population. Studies with a larger number of patients are required to further elucidate the role of DM on the PK-PD profile of first-line antitubercular drugs and treatment outcomes in TB patients with concomitant DM.

Trial registration

CTRI/2021/08/035578 dated 11/08/2021.

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一线抗结核药物的药代动力学-药效学：对伴有和不伴有糖尿病的结核病患者的比较研究

目的观察有糖尿病（DM）和无糖尿病（DM）的肺结核（TB）患者血浆浓度和一线抗结核药物的药代动力学-药效学（PK-PD）曲线的变化。第一组（20 人）包括肺结核患者，第二组（20 人）包括肺结核和糖尿病患者。治疗 2 周后，测定血浆浓度和其他 PK-PD 参数。治疗 2 个月后，对临床特征、X 光检查结果、痰液转阴率和药物不良反应（ADRs）的改善情况进行了评估。利福平在糖尿病患者中 4、8 和 12 小时的血浆浓度明显降低（P < 0.05），曲线下面积（AUC0-12 和 AUC0-∞）明显降低（P < 0.05），t1/2 更短，清除率（Cl）更高，AUC0-∞/MIC 比值更低。吡嗪酰胺和乙胺丁醇在糖尿病患者中的血浆浓度、AUC0-12、AUC0-∞和t1/2均无明显升高。结论在印度人群中，结核病患者中存在的 DM 会对异烟肼、利福平、吡嗪酰胺和乙胺丁醇的 PK-PD 参数产生不同程度的影响。需要对更多患者进行研究，以进一步阐明DM对一线抗结核药物PK-PD参数的影响以及合并DM的肺结核患者的治疗效果。

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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.