Exposure to rifampicin is strongly reduced in patients with tuberculosis and type 2 diabetes

Background. Type 2 diabetes (DM) is a strong risk factor for tuberculosis (TB) and is associated with a slower response to TB treatment and a higher mortality rate. Because lower concentrations of anti-TB drugs may be a contributing factor, we compared the pharmacokinetics of rifampicin in patients with TB, with and without DM. Methods. Seventeen adult Indonesian patients with TB and DM and 17 age- and sex-matched patients with TB and without DM were included in the study during the continuation phase of TB treatment. All patients received 450 mg of rifampicin (10 mg/kg) and 600 mg of isoniazid 3 times weekly. Steady-state plasma concentrations of rifampicin and its metabolite desacetylrifampicin were assessed at 0, 2, 4, and 6 h after drug intake. Results. Geometric means of rifampicin exposure (AUC_{0-6 h}) were 12.3 mg × h/L (95% confidence interval [CI], 8.0-24.2) in patients with TB and DM, and 25.9 mg × h/L (95% CI, 21.4-40.2) in patients with TB only (P = .003). Similar differences were found for the maximum concentration of rifampicin. No significant differences in time to maximum concentration of rifampicin were observed. The AUC_{0-6 h} of desacetylrifampicin was also much lower in patients with TB and DM versus patients with TB only (geometric mean, 0.60 vs. 3.2 mg × h/L; P = .001). Linear regression analysis revealed that higher body weight (P < .001), the presence of DM (P = .06), and plasma glucose concentration (P = .016) were correlated with exposure to rifampicin. Conclusion. Exposure (AUC_{0-6 h}) to rifampicin was 53% lower in Indonesian patients with TB and DM, compared with patients with TB only. Patients with TB and DM who have a higher body weight may need a higher dose of rifampicin.