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.
Piekoszewski
W
W
Department of Toxicology, Collegium Medicum, Jagiellonian University, Kraków, Poland.
Rutkowska
A
A
Brandys
J
J
D000818:Animals; D000983:Antipyrine / Q000008:administration & dosage / Q000378:metabolism*; D001711:Biotransformation; D002849:Chromatography, Gas; D002927:Cimetidine / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D002927:Cimetidine; D000983:Antipyrine