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Comparative effects of famotidine and cimetidine on antipyrine kinetics in healthy volunteers.

Cimetidine inhibits the metabolism of many drugs that are metabolized by the hepatic mixed' function oxidase system. There is evidence to suggest that not all H21-receptor antagonists (i.e. the furan-derivative ranitidine) share this property. Famotidine (MK-208) is a new H2-receptor antagonist with the amidine structure of the side chain of thiazole (Takagi et al., 1982). 40 mg of this H2-receptor blocker, given at bedtime, is as effective as 300 mg ranitidine nocte at decreasing 24-h intragastric acidity in healthy volunteers (Dammann et al., 1983). The efficacy of famotidine (2 x 20 mg daily vs 1 x 40 mg nocte) in the treatment of peptic ulcer disease is currently under clinical evaluation. As the metabolism of antipyrine has become generally accepted as meaningful index of hepatic P450 enzyme activity, we studied in a randomized order its pharmacokinetics after a 5 days treatment period with placebo, 1000 mg/day of cimetidine and 40 mg/day of famotidine, respectively in seven healthy volunteers (three male; mean age 27 years). Antipyrine plasma levels were determined at Day5 atO, 2, 4, 6, 8, 10, 12, 24, 30and36h after ingestion of 15 mg/kg b.w. oral antipyrine. Antipyrine was measured by high pressure liquid chromatography according to DeVries et al. (1984). The pharmacokinetic parameters were calculated according to Ritschel (1976) Wilcoxon-test for paired samples was applied. The data are given as mean + s.e. mean and are shown in Table 1. This study was approved by the Ethical Committee. All the volunteers gave their written informed consent to the study. Famotidine did not significantly affect the disposition of antipyrine in these subjects. In contrast, a prolongation of antipyrine half-life and diminution of antipyrine-clearance by about 22% could be demonstrated after cimetidine. Our data indicate that famotidine like the other guanidinothiazole containing compound tiotidine (which has been abandoned in the mean time) appears to be free from this unwanted effect on antipyrine-pharmacokinetics (Staiger etal., 1981).