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 x h/ L ( 95% confidence interval [CI], 8.0 - 24.2) in patients with TB and DM, and 25.9 mg x h/L ( 95% CI, 21.4 - 40.2) in patients with TB only (). 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 x h/L;). 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