Effects of food and formulation on the relative bioavailability of bismuth biskalcitrate, metronidazole, and tetracycline given for Helicobacter pylori eradication.
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.
Spénard
Jean
J
Axcan Pharma Inc., Mont-Saint-Hilaire, Montreal, Canada. jspenard@axcan.com
Aumais
Christian
C
Massicotte
Julie
J
Brunet
Jean-Sébastien
JS
Tremblay
Claude
C
Grace
Michael
M
Lefebvre
Marc
M
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
D000863:Antacids; D000900:Anti-Bacterial Agents; D004338:Drug Combinations; D008795:Metronidazole; D013752:Tetracycline; D001729:Bismuth