title: Influence of ranitidine, pirenzepine, and aluminum magnesium hydroxide on the bioavailability of various antibiotics, including amoxicillin, cephalexin, doxycycline, and amoxicillin-clavulanic acid.
abstract: Two randomized double-blind crossover studies and one randomized crossover study were performed to document possible drug-drug interactions between antacids (aluminum magnesium hydroxide, 10 ml per dose for 10 doses), antimuscarinic drugs (pirenzepine, 50 mg per dose for 4 doses), and H2-blockers (ranitidine, 150 mg per dose for 3 doses) and amoxicillin (1,000 mg), cephalexin (1,000 mg), doxycycline (200 mg), and amoxicillin-clavulanic acid (625 mg). Ten healthy volunteers participated in each study. Concentrations in serum and urine were measured by bioassay, and pharmacokinetic parameters were calculated by the usual open one- or two-compartment models (statistics were determined by the Wilcoxon test). The antacid, pirenzepine, and ranitidine had no influence on the bioavailability of amoxicillin, cephalexin, and amoxicillin-clavulanic acid. Only small differences could be observed in the pharmacokinetic parameters, but they are not of therapeutic importance. However, the antacid caused a significant (P less than 0.01) reduction in the gastrointestinal absorption of doxycycline (area under the concentration-time curve, 38.6 +/- 22.7 mg.h/liter, fasting; 6.0 +/- 3.2 mg.h/liter, with antacid), resulting in subtherapeutic levels of doxycycline.
authors.affiliation: Medical Department, Klinikum Steglitz, Freie Universität Berlin, Federal Republic of Germany.
authors.forename: K M
authors.initials: KM
authors.lastname: Deppermann
authors.forename: H
authors.initials: H
authors.lastname: Lode
authors.forename: G
authors.initials: G
authors.lastname: Höffken
authors.forename: G
authors.initials: G
authors.lastname: Tschink
authors.forename: C
authors.initials: C
authors.lastname: Kalz
authors.forename: P
authors.initials: P
authors.lastname: Koeppe
mesh_terms: D000328:Adult; D000536:Aluminum Hydroxide / Q000494:pharmacology*; D000658:Amoxicillin / Q000493:pharmacokinetics; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics*; D001682:Biological Availability; D002506:Cephalexin / Q000493:pharmacokinetics; D002969:Clavulanic Acids / Q000493:pharmacokinetics; D004318:Doxycycline / Q000493:pharmacokinetics; D004338:Drug Combinations / Q000494:pharmacology; D004347:Drug Interactions; D005260:Female; D006801:Humans; D008274:Magnesium / Q000494:pharmacology*; D008276:Magnesium Hydroxide / Q000494:pharmacology*; D008297:Male; D010890:Pirenzepine / Q000494:pharmacology*; D011899:Ranitidine / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D002969:Clavulanic Acids; D004338:Drug Combinations; C013591:aluminum hydroxide, magnesium hydroxide, drug combination; D010890:Pirenzepine; D000536:Aluminum Hydroxide; D000658:Amoxicillin; D011899:Ranitidine; D008274:Magnesium; D004318:Doxycycline; D008276:Magnesium Hydroxide; D002506:Cephalexin