title: Influence of omeprazole on bioavailability of bismuth following administration of a triple capsule of bismuth biskalcitrate, metronidazole, and tetracycline.
abstract: The objective of this study was to determine the impact of omeprazole on bismuth (Bi) bioavailability when given in a three-in-one capsule containing bismuth biskalcitrate, metronidazole, and tetracycline. Thirty-four healthy volunteers were randomly assigned to receive three capsules (each containing bismuth biskalcitrate 140 mg + metronidazole 125 mg + tetracycline 125 mg) qid alone x 6 days or the same treatment + omeprazole (OM) 20 mg bid. Blood was drawn at intervals for 24 hours after the last dose. After the last dose, mean (CV) C(min) for plasma bismuth was 2882 pg/mL (36%) and 1195 pg/mL (23%) (p< 0.001), with and without OM, respectively. Mean (CV) C(max) was 25493 pg/mL (69%) and 8061 pg/mL (28%) (p < 0.001) with and without OM, respectively. AUC(0-24) increased by 2.9 in presence of OM (p < 0.001). Adverse events in both groups were usually mild and of a gastrointestinal nature, and all had resolved by the end of the trial. This study confirms an interaction between Bi biskalcitrate and OM. Risk of Bi toxicity, seen after long-term use of Bi compounds, is minimal here because plasma levels of Bi remained well below the toxic levels of 50 microg/L, and the treatment period with this triple capsule + OM is only 10 days, a substantially lower number of days compared to that which might produce Bi toxicity.
authors.affiliation: Axcan Pharma, Inc, 597 boul Laurier, Mont-Saint-Hilaire Qc, Canada J3H 6C4.
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: Claude
authors.initials: C
authors.lastname: Tremblay
authors.forename: Marc
authors.initials: M
authors.lastname: Lefebvre
mesh_terms: D000328:Adult; D000890:Anti-Infective Agents / Q000008:administration & dosage; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D019540:Area Under Curve; D001682:Biological Availability; D004347:Drug Interactions; D004357:Drug Synergism; D006207:Half-Life; D006801:Humans; D008297:Male; D008795:Metronidazole / Q000008:administration & dosage; D008875:Middle Aged; D009853:Omeprazole / Q000494:pharmacology*; D009942:Organometallic Compounds / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D013752:Tetracycline / Q000008:administration & dosage
chemical_list: D000890:Anti-Infective Agents; D000897:Anti-Ulcer Agents; D009942:Organometallic Compounds; D008795:Metronidazole; D013752:Tetracycline; C002791:bismuth tripotassium dicitrate; D009853:Omeprazole