TO THE EDITOR:
Recent studies indicate that cimetidine and ranitidine, but not famotidine, may inhibit gastric alcohol-dehydrogenase activity, thus impairing the gastric first-pass metabolism of ethanol [1-4]. Those studies, however, were done in "artificial" conditions (healthy patients; 1 week of treatment; last dose at breakfast, 1 hour before alcohol ingestion). We studied whether prolonged treatment with ranitidine or famotidine affected blood alcohol concentrations in 16 men with duodenal ulcers. Patients with Helicobacter pylori-associated duodenal ulcers were not enrolled [5]. Patients were randomly assigned to receive either 300 mg of ranitidine (n = 8) or 40 mg of famotidine (n = 8) at bedtime for 2 months. The rate of gastric first-pass metabolism was checked in all patients before study entry and was found to be 53% by comparing the area under the curve (AUC) of blood alcohol concentration after either intravenous or oral administration of 0.3 g/kg of ethanol (AUC [intravenous] = 11.6 ±1.6 mM/h; AUC [oral] = 5.4 ±0.6 mM/h). Patients had a standard lunch (at 1:00 p.m.), and 0.3 g/kg of alcohol was consumed 15 minutes after the meal. Blood alcohol concentrations were measured by a gas-chromatographic procedure up to 150 minutes after drinking alcohol. Ranitidine did not significantly modify either the mean oral AUC (5.8 ±1.8 mM/h before treatment compared with 6.2 ±1.4 mM/h after treatment) or the peak blood alcohol concentration (4.6 ±1.1 mM compared with 5.3 ±1.7 mM) after 2 months of treatment. Famotidine failed to affect blood alcohol concentration in the second group of patients (AUC [oral] = 5.0 ±1.4 mM/h compared with 5.6 mM/h ±1.7 mM/h, peak blood alcohol concentration = 4.0 mM ±1.7 mM compared with 4.3 mM ±1.8 mM; before and after treatment, respectively). No significant differences in alcohol-dehydrogenase activity were found in the gastric mucosal biopsy specimens of patients after treatment with either drug. Although ranitidine and some other histamine-2-receptor antagonists have been clearly shown to inhibit gastric alcohol-dehydrogenase activity in vitro, our results suggest that these studies may not be clinically relevant.
1. Julkunen RJ, DiPadova C, Lieber CS. First pass metabolism of ethanol: a gastrointestinal barrier against the systemic toxicity of ethanol. Life Sci. 1985; 37:567-73.
2. Hernandez-Mugnoz R, Caballeria J, Baraona E, Uppal R, Greenstein R, Lieber CS. Human gastric alcohol dehydrogenase: its inhibition by H2-receptor antagonists, and its effect on the bioavailability of ethanol. Alcohol Clin Exp Res. 1990; 14:946-50.
3. Caballeria J, Baraona E, Deulofeu R, Hernandez-Munoz R, Rodes J, Lieber CS. Effects of H2-receptor antagonists on gastric alcohol dehydrogenase activity. Dig Dis Sci. 1991; 36:1673-9.
4. DiPadova C, Roine R, Frezza M, Gentry RT, Baraona E, Lieber CS. Effects of ranitidine on blood alcohol levels after ethanol ingestion. JAMA. 1992; 267:83-6.
5. Roine R, Salmela KS, Hook-Nikanne J, Kosunen TU, Salaspuro M. Alcohol dehydrogenase mediated acetaldehyde production by Helicobacter pylori. A possible mechanism behind gastric injury. Life Sci. 1992; 51:1333-7.
Top
Author & Article Info
References
Article
