Significant Increase of Blood Alcohol by Cimetidine after Repetitive Drinking of Small Alcohol Doses

Abstract

To assess effects of repetitive alcohol drinking and pre-existing first-pass metabolism on the cimetidine-induced increase in blood alcohol concentrations, 20 healthy men (aged 20 to 40) of varied ethnicity and consuming less than 60 g alcohol per week underwent baseline quantitation of first-pass metabolism of alcohol. This was followed by oral administration of 0.6 g/kg ethanol given postprandially in 3 to 4 drinks spread over 135 min, before and after cimetidine (400 mg twice a day for 7 days). Blood alcohol concentrations were determined by breath analysis. First-pass metabolism was quantified by applying Michaelis-Menten kinetics to blood alcohol curves after intravenous or oral administration of equal alcohol doses. At baseline, 15 subjects had a substantial first-pass metabolism (over one sixth of the dose); their alcohol levels increased with repeated doses with a mean peak of 27 +/- 3 mg/dl before and 39 +/- 5 after cimetidine (P < 0.01), an effect much greater and longer than after a single alcohol dose. Three subjects exceeded 50 mg/dl, the legal limit for driving in several countries. By contrast, in the five subjects with minimal first-pass metabolism, cimetidine did not increase alcohol levels. Thus, under conditions mimicking social drinking, cimetidine increased blood alcohol to concentrations known to impair psychomotor skills and they persisted at those levels over prolonged periods of time. In a minority of subjects, no such interaction was found, but their first-pass metabolism at baseline was absent or minimal and thus no inhibition by the drug was to be expected.

Gender Differences in Pharmacokinetics of Alcohol

“…When blood alcohol levels reach zero, the amount eliminated is equal to that which entered the systemic blood. These quantities were calculated by integration of the Michaelis-Menten equation over the entire curve of blood alcohol concentrations, as previously described in detail (Dohmen et al, 1996;Gentry et al, 1992;Gupta et al, 1995). The maximal rate of elimination (VMAX), the ethanol concentration at half maximal velocity (KM), and the volume of alcohol distribution (VD) were obtained in each subject by curve fitting of the Michaelis-Menten function to the descending blood alcohol levels after intravenous injection of ethanol.…”

“…Breath analysis was previously validated with direct measurements of blood ethanol by head-space gas chromatography (Gupta et al, 1995).…”

Handbook of Drug Interactions

“…Diltiazem has been shown to inhibit the elimination of intravenous [306] and oral [307] midazolam and oral triazolam [308,309]. Verapamil inhibits the elimination of midazolam [307], and mibefradil the elimination of triazolam [310].…”

Conversation with Charles S. Lieber

“…67 Although we focused on MEOS, we did not neglect ADH. Gender differences were de ned 68 as well as the contribution of the stomach ADH to the rst-pass metabolism of ethanol, 69,70 the cloning of the gene of a new ADH isozyme, namely Sigma ADH, 71 its localization to chromosome 4, as well as the increased blood alcohol levels through inhibition of the gastric rst-pass metabolism 69,70 or the acceleration of gastric emptying 72 by commonly used H 2 blockers. [69][70][71][72][73] Experimental and clinical nutrition A: You have also had a great interest in the area of alcohol and nutrition.…”