FAMOTIDINE INCREASES PLASMA ALCOHOL CONCENTRATION IN HEALTHY-SUBJECTS

The effect of famotidine on plasma alcohol concentration was studied i n 24 healthy male subjects who demonstrated high apparent ethanol firs t-pass metabolism after oral (p.o.) and intravenous (i.v.) ethanol adm inistration (i.e. AUC(po) less-than-or-equal-to 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 firs t-pass metabolism and were excluded. In a randomized open crossover st udy, oral ethanol pharmacokinetics were assessed after breakfast in th e morning following a 3-day regimen of famotidine, 40 mg/day, and foll owing a no-drug control period. Famotidine increased the area under th e plasma ethanol concentration-time curve (AUC0-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 AUC0-t and C(max ) may have been associated with changes in gastric emptying, as they w ere inversely correlated with changes in the time at which maximal pla sma concentration was attained. There was considerable intra-individua l variation in ethanol AUC and C(max). As a result, regression to the mean is a potentially confounding problem in ethanol pharmacokinetic s tudies when subjects are selected on the basis of having low AUC(po) a nd properly controlled randomized studies of substantial size are requ ired to detect modest drug effects. Small effects on ethanol pharmacok inetics have now been demonstrated with all four of the major H-2-rece ptor antagonists, but these effects are seen only under specific exper imental conditions and appear to be unimportant clinically.