Effects of food and formulation on the relative bioavailability of bismuth biskalcitrate, metronidazole, and tetracycline given for Helicobacter pylori eradication

Aims 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 × 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 Cmax, AUCt, and AUC∞. Results With respect to food, none of the three drugs met bioequivalence guidelines. Bismuth had lower limit CIs ranging from 12% for Cmax to 25% for AUC∞. The corresponding values for tetracycline were 59% and 51%. Metronidazole had a lower limit CI of 74% for Cmax. With respect to formulation, bismuth had lower limits of CIs ranging from 39% for Cmax to 50% for AUCt and higher limits of 146% for AUCt, metronidazole met bioequivalence guidelines, and tetracycline had lower limits of CIs between 72% for AUCt and 74% for AUC∞. 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.