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

Hanneke M.J. Nijland, Rovina Ruslami, Janneke E. Stalenhoef, Erni Juwita, Bachti Alisjahbana, Ron H.H. Nelwan, Andre J.A.M. Van Der Ven, Halim Danusantoso, Rob E. Aarnoutse, Reinout Van Crevel

Research output: Contribution to journalArticlepeer-review

162 Citations (Scopus)

Abstract

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 (AUC0-6 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 AUC0-6 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 (AUC0-6 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.

Original languageEnglish
Pages (from-to)848-854
Number of pages7
JournalClinical Infectious Diseases
Volume43
Issue number7
DOIs
Publication statusPublished - 1 Oct 2006

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