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

Abstract

Purpose To observe the variability in the plasma concentrations and pharmacokinetic-pharmacodynamic (PK-PD) profile 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 with or without DM were included in the study. Group I (n = 20) included patients with TB, whereas Group II (n = 20) contained patients with TB and DM. After 2 weeks of therapy, plasma concentrations and other PK-PD parameters were determined. The improvement in clinical features, X-ray findings, sputum conversion and adverse drug reactions (ADRs) were measured after 2 months of ATT. 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 concentration at 4, 8, and 12 h were significantly (P < 0.05) lower and it displayed significantly (P < 0.05) lower area under curves (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 improvement in clinical features, X-ray findings, sputum conversion, and ADRs were comparable in both the 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 in 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 number CTRI/2021/08/035578 dated 11/08/2021.