Induction of the rat hepatic microsomal mixed-function oxidases by cimetidine.
The ability of cimetidine to induce the hepatic microsomal mixed-function oxidases was investigated in rats treated orally with the drug at 3 dose levels: 10, 100 and 500 mg/kg. At the highest dose only, cimetidine stimulated the dealkylations of ethoxyresorufin, ethoxycoumarin and pentoxyresorufin but inhibited that of erythromycin and had no effect on the demethylation of dimethylnitrosamine. At the highest dose cimetidine had a small effect on the activation of Glu-P-1 to mutagens in the Ames test but induced proteins recognised in Western blots by antibodies to P450 I A1 and P450 II B1. It is concluded that cimetidine is a weak selective inducer of cytochrome P-450 forms, but at therapeutic doses its inductive effect is most unlikely to be of any clinical or toxicological consequence.
Ioannides
C
C
Department of Biochemistry, University of Surrey, Guildford, U.K.
Rodrigues
A D
AD
Ayrton
A D
AD
Barnett
C R
CR
Chown
J
J
Parke
D V
DV
D000818:Animals; D001711:Biotransformation; D002927:Cimetidine / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis; D003640:Dealkylation; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction / Q000187:drug effects; D007093:Imidazoles / Q000378:metabolism; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects* / Q000201:enzymology; D006899:Mixed Function Oxygenases / Q000096:biosynthesis*; D009152:Mutagenicity Tests; D051381:Rats; D011919:Rats, Inbred Strains
D007093:Imidazoles; C023785:2-amino-6-methyldipyrido(1,2-a-3',2'-d)imidazole; D002927:Cimetidine; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases