title: Elevated gatifloxacin and reduced rifampicin concentrations in a single-dose interaction study amongst healthy volunteers.
abstract: OBJECTIVE
  Pharmacokinetic drug-drug interactions were investigated between the fluoroquinolone gatifloxacin and a fixed dose combination (FDC) of rifampicin, isoniazid and pyrazinamide.
  
  
  METHODS
  The single-dose pharmacokinetics of the four drugs was evaluated in an open-label three-way cross-over study amongst 22 healthy volunteers following administration of gatifloxacin, the FDC or the two products together.
  
  
  RESULTS
  Modest but potentially important drug-drug interactions affecting gatifloxacin and rifampicin concentrations were detected. The elimination rate of gatifloxacin was reduced such that the AUC from 0 h to infinity was increased with a geometric mean ratio (GMR) [90% confidence interval (CI)] of 1.14 (1.10, 1.18). Conversely, the AUC from 0 h to infinity for rifampicin was reduced (GMR: 0.81, 90% CI: 0.81, 0.96) when rifampicin, isoniazid and pyrazinamide were given together with gatifloxacin.
  
  
  CONCLUSIONS
  Studies in patients including pharmacokinetic evaluation at steady state, efficacy and toxicity are required to determine the importance of the interactions for use of the combination of gatifloxacin, rifampicin, isoniazid and pyrazinamide in the treatment of tuberculosis.
authors.affiliation: Division of Clinical Pharmacology, Department of Medicine, Groote Schuur Hospital, University of Cape Town, South Africa. helen.mcilleron@uct.ac.za
authors.forename: Helen
authors.initials: H
authors.lastname: McIlleron
authors.forename: Jennifer
authors.initials: J
authors.lastname: Norman
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Kanyok
authors.forename: P Bernard
authors.initials: PB
authors.lastname: Fourie
authors.forename: John
authors.initials: J
authors.lastname: Horton
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Smith
mesh_terms: D000368:Aged; D000904:Antibiotics, Antitubercular / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019540:Area Under Curve; D018592:Cross-Over Studies; D004347:Drug Interactions; D005260:Female; D024841:Fluoroquinolones / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000077734:Gatifloxacin; D006801:Humans; D007538:Isoniazid / Q000008:administration & dosage / Q000493:pharmacokinetics; D008297:Male; D008875:Middle Aged; D011718:Pyrazinamide / Q000008:administration & dosage / Q000493:pharmacokinetics; D012293:Rifampin / Q000008:administration & dosage / Q000493:pharmacokinetics*
chemical_list: D000904:Antibiotics, Antitubercular; D024841:Fluoroquinolones; D011718:Pyrazinamide; D000077734:Gatifloxacin; D007538:Isoniazid; D012293:Rifampin