title: Exposure to rifampicin is strongly reduced in patients with tuberculosis and type 2 diabetes.
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 (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.
  
  
  CONCLUSIONS
  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.affiliation: Department of Clinical Pharmacy, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
authors.forename: Hanneke M J
authors.initials: HM
authors.lastname: Nijland
authors.forename: Rovina
authors.initials: R
authors.lastname: Ruslami
authors.forename: Janneke E
authors.initials: JE
authors.lastname: Stalenhoef
authors.forename: Erni J
authors.initials: EJ
authors.lastname: Nelwan
authors.forename: Bachti
authors.initials: B
authors.lastname: Alisjahbana
authors.forename: Ron H H
authors.initials: RH
authors.lastname: Nelwan
authors.forename: Andre J A M
authors.initials: AJ
authors.lastname: van der Ven
authors.forename: Halim
authors.initials: H
authors.lastname: Danusantoso
authors.forename: Rob E
authors.initials: RE
authors.lastname: Aarnoutse
authors.forename: Reinout
authors.initials: R
authors.lastname: van Crevel
mesh_terms: D000328:Adult; D000995:Antitubercular Agents / Q000493:pharmacokinetics*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000302:isolation & purification; D012293:Rifampin / Q000493:pharmacokinetics*; D014376:Tuberculosis / Q000150:complications / Q000378:metabolism*
chemical_list: D000995:Antitubercular Agents; D012293:Rifampin