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.