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 (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 x 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.
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 (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 x 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.
Authors: Jonathan Chambers; Madhu Page-Sharp; Sam Salman; John Dyer; Timothy M E Davis; Kevin T Batty; Laurens Manning Journal: Eur J Clin Pharmacol Date: 2018-12-04 Impact factor: 2.953
Authors: Yuri F van der Heijden; Fareed Abdullah; Bruno B Andrade; Jason R Andrews; Devasahayam J Christopher; Julio Croda; Heather Ewing; David W Haas; Mark Hatherill; C Robert Horsburgh; Vidya Mave; Helder I Nakaya; Valeria Rolla; Sudha Srinivasan; Retna Indah Sugiyono; Cesar Ugarte-Gil; Carol Hamilton Journal: Tuberculosis (Edinb) Date: 2018-10-01 Impact factor: 3.131
Authors: Ben Knippenberg; Madhu Page-Sharp; Sam Salman; Ben Clark; John Dyer; Kevin T Batty; Timothy M E Davis; Laurens Manning Journal: Antimicrob Agents Chemother Date: 2016-07-22 Impact factor: 5.191
Authors: Julia A Critchley; Blanca I Restrepo; Katharina Ronacher; Anil Kapur; Andrew A Bremer; Larry S Schlesinger; Randall Basaraba; Hardy Kornfeld; Reinout van Crevel Journal: Chest Date: 2017-04-20 Impact factor: 9.410