, Volume 36, Issue 1, pp 25-28

Enhancement of antibiotic concentrations in gastric mucosa by H2-receptor antagonist

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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 (81.5μg/g vs 15.9μg/g;P<0.05) and 10-fold greater at 2 hr (82.7μg/g vs 8.09μg/g;P<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 inH. pylori infections by virtue of increasing gastric concentrations of antibiotics that behave as weak bases.

Sponsored in part by Public Health Service grant RR05870 from the National Institutes of Health and by Upjohn Company.