Famotidine increases plasma alcohol concentration in healthy subjects

The effect of famotidine on plasma alcohol concentration was studied in 24 healthy male subjects who demonstrated high apparent ethanol first-pass metabolism after oral (p.o.) and intravenous (i.v.) ethanol administration (i.e. AUC_po S 40% of AUC_iv, where AUC is area under the plasma ethanol concentration-time curve). Six of the original 30 subjects screened (20%) did not demonstrate high first-pass metabolism and were excluded. In a randomized open crossover study, oral ethanol pharmacokinetics were assessed after breakfast in the morning following a 3-day regimen of famotidine, 40 mg/day, and following a no-drug control period. Famotidine increased the area under the plasma ethanol concentration-time curve (AUC_0-t) by 29% (7.1 vs 5.5 mg.h/dL, P= 0.006) and maximal plasma concentration (C_max) by 23% (9.2 vs 7.5 mg/dL, P= 0.013). The changes in ethanol AUC_0-t and C_max may have been associated with changes in gastric emptying, as they were inversely correlated with changes in the time at which maximal plasma concentration was attained. There was considerable intra-individual variation in ethanol AUC and C_max. As a result, regression to the mean is a potentially confounding problem in ethanol pharmacokinetic studies when subjects are selected on the basis of having low AUC_po, and properly controlled randomized studies of substantial size are required to detect modest drug effects. Small effects on ethanol pharmacokinetics have now been demonstrated with all four of the major H₂-receptor antagonists, but these effects are seen only under specific experimental conditions and appear to be unimportant clinically.