title: Low plasma concentrations of rifampicin in tuberculosis patients in Indonesia.
abstract: METHODS
  Although rifampicin is a key drug in tuberculosis treatment, little is known about its quality and bioavailability in countries endemic for tuberculosis. High drug levels may lead to increased toxicity, while low drug levels may predispose to treatment failure and relapse.
  
  
  OBJECTIVE
  To investigate possible variations in the bioavailability of plasma rifampicin in tuberculosis patients in Indonesia.
  
  
  METHODS
  Plasma concentrations of rifampicin and the rifampicin content of drug formulations in use were measured among 62 non-selected tuberculosis patients in Jakarta, Indonesia.
  
  
  RESULTS
  Plasma concentrations of rifampin were generally low: 70% of patients had 2-hour plasma concentrations (Cmax) below 4 mg/L. No toxic plasma concentrations of rifampicin (>20 mg/L) were found. The strongest predictive factor for the magnitude of rifampicin concentrations was the drug manufacturer. The rifampicin content of the different drug preparations used was normal (90.5-103.6% of the reference standard). No association was found between low plasma rifampicin concentrations and delayed sputum conversion or treatment failure.
  
  
  CONCLUSIONS
  The unexpectedly low plasma concentrations of rifampicin in this setting are most likely due to reduced bioavailability of local drug preparations, as the rifampicin content of the drug preparations was found to be normal. The clinical significance of these findings remains to be determined.
authors.affiliation: Department of Internal Medicine, University Medical Centre Nijmegen, The Netherlands. r.vancrevel@aig.azn.nl
authors.forename: R
authors.initials: R
authors.lastname: van Crevel
authors.forename: B
authors.initials: B
authors.lastname: Alisjahbana
authors.forename: W C M
authors.initials: WC
authors.lastname: de Lange
authors.forename: F
authors.initials: F
authors.lastname: Borst
authors.forename: H
authors.initials: H
authors.lastname: Danusantoso
authors.forename: J W M
authors.initials: JW
authors.lastname: van der Meer
authors.forename: D
authors.initials: D
authors.lastname: Burger
authors.forename: R H H
authors.initials: RH
authors.lastname: Nelwan
mesh_terms: D000293:Adolescent; D000328:Adult; D000904:Antibiotics, Antitubercular / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical; D005260:Female; D006801:Humans; D007214:Indonesia; D008297:Male; D008875:Middle Aged; D012293:Rifampin / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy*
chemical_list: D000904:Antibiotics, Antitubercular; D012293:Rifampin