LETTER
Blood Alcohol Levels after Prolonged Use of Histamine-2-Receptor Antagonists
Enrique Baraona, MD;
R. Thomas Gentry, PhD; and
Charles S. Lieber, MD
1 July 1994 | Volume 121 Issue 1 | Pages 73-74
TO THE EDITOR:
The lack of interaction between ranitidine and blood alcohol reported by Casini and colleagues [1] in eight patients with duodenal ulcer does not invalidate the many studies showing that histamine-2 (H2)-receptor antagonists (including ranitidine) increase blood alcohol concentrations with small alcohol doses (150 mg/kg) [2]. A prerequisite for the effect is a substantial first-pass metabolism of ethanol because these H2-blockers, found to inhibit gastric alcohol dehydrogenase, probably act by decreasing the first-pass metabolism. Several factors (for example, fasting or alcoholism) decrease first-pass metabolism; even in 20% of normal patients, it is minimal or absent for unknown reasons [3]. Inclusion of such persons may have produced the reported inconclusive results [1]. This possibility has not been ruled out in Casini and colleagues' patients because comparison of areas-under-the-curve after oral and intravenous ethanol is inappropriate to quantify first-pass metabolism after an alcohol dose (such as 300 mg/kg). First-pass metabolism can be quantified using the Michaelis-Menten kinetics of alcohol elimination [4]. Moreover, patients taking these drugs for minor dyspeptic symptoms are more likely than are their study patients with ulcers to engage in social drinking, (repetitive consumption of small alcohol doses). We have recently shown that under these conditions, the effects of first-pass metabolism inhibition by some H2-blockers on blood alcohol concentration are cumulative [5]. As a result, blood alcohol concentration can increase to levels known to impair mental function and driving capacity and thus can become clinically relevant.
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Author and Article Information
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Mt. Sinai School of Medicine; New York, NY 10468
1. Casini A, Mari F, Surrenti C. Blood alcohol levels after prolonged histamine-2-receptor antagonist treatment (Letter). Ann Intern Med. 1994; 120:90.
2. Roine R, Hernandez-Munoz R, Baraona E, Gentry RT, Lieber CS. H (2) antagonists and blood alcohol levels (Letter). Dig Dis Sci. 1993; 38:572-73.
3. Gentry RT, Baraona E, Lieber CS. Gastric first-pass metabolism of alcohol. J Lab Clin Med. 1994; 123:21-6.
4. Gentry TR, Sharma R, Lim RT, Baraona E, DiPadova C, Lieber CS. A new method to quantify first pass metabolism of alcohol: Application to the effects of H2-blockers on alcohol bioavailability (Abstract). Gastroenterology. 1992; 92:A811.
5. Gupta AM, Baraona E, Lieber CS. Potentiation of the cimetidine-induced increase in blood alcohol levels after repeated small ethanol doses. Alcoholism: Clin Exp Res. 1994 (In press).
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