Comparative effects of famotidine and cimetidine on 7‐ethoxycoumarin O‐ deethylase activity in human livers [letter]

Cimetidine, one of the histamine H2-receptor antagonists, has been shown to bind to hepatic microsomal cytochrome P-450 and inhibit drug metabolism in humans and animals because of its imidazole ring and side chain structure (Serlin et al., 1979; Henry et al., 1982; Rendic et al., 1983). Famotidine, a new potent histamine H2receptor antagonist (Takagi et al., 1982) has a thiazole ring with a side chain of amidine structure and has been reported to be free from inhibitory effect on antipyrine pharmacokinetics in healthy subjects (Staiger et al., 1984). We compared the effect of famotidine with that of cimetidine on hepatic microsomal drug metabolism in human liver biopsy specimens. Cytochrome P-450 linked drug metabolism was evaluated by 7-ethoxycoumarin O-deethylase activity according to the method of Greenlee et al. (1978). Liver biopsy specimens were obtained under laparoscopic control with a VimSilvermann needle for histological examinations and part of each specimen (25-50 mg wet weight) were used for the assay. Histology of the samples showed chronic persistent hepatitis or mild fatty infiltration. Each biopsy specimen was tested with a range of famotidine and cimetidine concentrations. The reaction mixture consisted of liver homogenate, 7-ethoxycoumarin (0.5 mM) andNADPH generating system (NADPH lmM, glucose 6-phosphate dehydrogenase 1 unit and glucose 6-phosphate 2 mM) in a final volume of 50mM phosphate buffer pH 7.4. The incubation time was 15 min. Famotidine and cimetidine dissolved in dimethylsuphoxide were added in the reaction mixture and the same volume of the solvent was added in the control assay. Our results (Table 1) on cimetidine were similar to those reported by Puurunen et al. Table 1 Inhibition by famotidine and cimetidine of 7-ethoxycoumarin O-deethylase activity in human liver biopsy samples (n = 6)