title: Enhancement of antibiotic concentrations in gastric mucosa by H2-receptor antagonist. Implications for treatment of Helicobacter pylori infections.
abstract: We measured the effects of cimetidine on antibiotic concentrations in the luminal portion of gastric mucosa. Guinea pigs were premedicated with cimetidine 4 mg/kg intramuscularly. Clindamycin, an antibiotic previously characterized under physiologic pH conditions, was administered intramuscularly and levels measured in serum and tissue using a high-pressure liquid chromatography (HPLC) technique. The luminal mucosa concentration of clindamycin at 1 hr (pH 5.9) was fivefold greater compared to the concentrations seen under physiologic (pH 2.0) conditions (81.5 micrograms/g vs 15.9 micrograms/g; P less than 0.05) and 10-fold greater at 2 hr (82.7 micrograms/g vs 8.09 micrograms/g; P less than 0.05). There was no difference in peak serum levels between the groups. The finding that an antibiotic with characteristics of a base is thus affected by a nonconservative acid inhibitor such as cimetidine supports the presence of an acidic storage pool as proposed by other investigators. H2-receptor antagonists may be useful therapeutic adjuncts in H. pylori infections by virtue of increasing gastric concentrations of antibiotics that behave as weak bases.
authors.affiliation: Department of Medicine, St. Louis University, Missouri.
authors.forename: T U
authors.initials: TU
authors.lastname: Westblom
authors.forename: D E
authors.initials: DE
authors.lastname: Duriex
mesh_terms: D000136:Acid-Base Equilibrium / Q000187:drug effects; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D002927:Cimetidine / Q000494:pharmacology*; D002981:Clindamycin / Q000493:pharmacokinetics* / Q000627:therapeutic use; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism*; D006168:Guinea Pigs; D016481:Helicobacter Infections / Q000188:drug therapy*; D016480:Helicobacter pylori / Q000187:drug effects*
chemical_list: D002981:Clindamycin; D002927:Cimetidine