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

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). 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 and AUC), shorter t, higher clearance (Cl), and a lower AUC/MIC ratio in diabetic patients. Pyrazinamide and ethambutol showed non-significantly higher plasma concentrations, AUC, AUC, and t 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.