title: Effects of food and formulation on the relative bioavailability of bismuth biskalcitrate, metronidazole, and tetracycline given for Helicobacter pylori eradication.
abstract: OBJECTIVE
  To evaluate the effects of food and formulation on the pharmacokinetics of bismuth biskalcitrate, metronidazole and tetracycline when combined in a new 3-in-1 single capsule (BMT) for eradication of Helicobacter pylori.
  
  
  METHODS
  In a randomized, 3 x 3 cross-over design, 23 healthy males received one dose of BMT in the fed and fasting states and equivalent doses of the three drugs given together but as separate capsules while fasting. Bioequivalence was evaluated according to 90% confidence intervals (CIs) of ratios of geometric least square means for C(max), AUC(t), and AUC(infinity).
  
  
  RESULTS
  With respect to food, none of the three drugs met bioequivalence guidelines. Bismuth had lower limit CIs ranging from 12% for C(max) to 25% for AUC(infinity). The corresponding values for tetracycline were 59% and 51%. Metronidazole had a lower limit CI of 74% for C(max). With respect to formulation, bismuth had lower limits of CIs ranging from 39% for C(max) to 50% for AUC(t) and higher limits of 146% for AUC(t), metronidazole met bioequivalence guidelines, and tetracycline had lower limits of CIs between 72% for AUC(t) and 74% for AUC(infinity).
  
  
  CONCLUSIONS
  Food significantly decreased the relative bioavailability of each drug but formulation was without effect. This decrease may be beneficial when a local gastric action is needed, as confirmed by a near 90% eradication rate when this combined capsule is administered with food to treat gastro-duodenal local infection by H. pylori.
authors.affiliation: Axcan Pharma Inc., Mont-Saint-Hilaire, Montreal, Canada. jspenard@axcan.com
authors.forename: Jean
authors.initials: J
authors.lastname: Spénard
authors.forename: Christian
authors.initials: C
authors.lastname: Aumais
authors.forename: Julie
authors.initials: J
authors.lastname: Massicotte
authors.forename: Jean-Sébastien
authors.initials: JS
authors.lastname: Brunet
authors.forename: Claude
authors.initials: C
authors.lastname: Tremblay
authors.forename: Michael
authors.initials: M
authors.lastname: Grace
authors.forename: Marc
authors.initials: M
authors.lastname: Lefebvre
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000863:Antacids / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001682:Biological Availability; D001729:Bismuth / Q000493:pharmacokinetics* / Q000627:therapeutic use; D018592:Cross-Over Studies; D004338:Drug Combinations; D018565:Food-Drug Interactions; D016481:Helicobacter Infections / Q000188:drug therapy*; D016480:Helicobacter pylori; D006801:Humans; D008297:Male; D008795:Metronidazole / Q000493:pharmacokinetics / Q000627:therapeutic use; D008875:Middle Aged; D013752:Tetracycline / Q000493:pharmacokinetics / Q000627:therapeutic use
chemical_list: D000863:Antacids; D000900:Anti-Bacterial Agents; D004338:Drug Combinations; D008795:Metronidazole; D013752:Tetracycline; D001729:Bismuth