IMPACT OF TYPE 2 DIABETES MELLITUS ON RIFAMPICIN PHARMACOKINETICS AND BIOCHEMICAL PATHWAYS IN PULMONARY TUBERCULOSIS PATIENTS

Background: The co-occurrence of pulmonary tuberculosis (PTB) and type 2 diabetes mellitus (T2DM) presents a significant public health challenge. T2DM may alter the pharmacokinetics (PK) of antitubercular drugs, particularly rifampicin, compromising therapeuticefficacy.Objective: To investigate the impact of T2DM on rifampicin PK and biochemical pathways in PTB patients.Methods: A prospective observational study was conducted involving 60 PTB patients (30 with T2DM and 30 non-diabetic controls). Plasma rifampicin concentrations were analyzed using LC-MS/MS at multiple time points post-dosing. Biochemical markers including CRP, IL-6, fasting glucose, and liver function tests were assessed. Non-compartmental PK analysis was performed.Results: Diabetic patients showed significantly delayed rifampicin Tmax (mean 3.1 h vs 2.2 h, p< 0.01) and reduced Cmax (6.8 ± 2.1 μg/mL vs 9.5 ± 2.6 μg/mL, p< 0.001). AUC₀–₂₄ was also lower in the T2DM group (48.2 ± 11.3 μg·h/mL vs 61.4 ± 10.7 μg·h/mL, p< 0.05). Higher levels of systemic inflammation (CRP, IL-6) correlated inversely with rifampicin exposure.Conclusion: T2DM significantly impairs rifampicin pharmacokinetics in PTB patients, likely through altered absorption and inflammatory modulation. Dose optimization and therapeutic drug monitoring (TDM) should be considered in this population