Inhibitory action of cimetidine on antipyrine metabolism.

The influence of cimetidine on the activity of microsomal enzymes in vivo using the simple one-sample antipyrine test was investigated. The calculated antipyrine clearance unequivocally indicates the dose-dependent effect of cimetidine on the microsomal biotransformation of antipyrine. The IC50 of cimetidine inhibitory effect was 39.9 mg/kg. The duration of the effect was approximately 12 h and the lowest antipyrine clearance was observed 0.5 h following cimetidine administration. The in vivo results were confirmed by an in vitro study. Km for global metabolic processes of antipyrine in vitro was 1.3 mM. Vmax 9.1 nM/mg/min for control was decreased to 3.1 nM/mg/min after addition of cimetidine (4 mM). The inhibition constant of cimetidine determined by the method of Dixon, was 2.8 mM. Inhibition of antipyrine metabolism by cimetidine was noncompetitive.