The effects of cimetidine, ranitidine and famotidine on rat hepatic microsomal cytochrome P-450 activities.
It has been questioned whether the interaction of H2-antagonists with cytochrome P-450 that is observed in vitro is also relevant for the in vivo situation. Until now the possibility that cytochrome P-450 may function with different modes of action has been neglected in this respect. We studied the effect of cimetidine, ranitidine and famotidine on the monoxygenase, the oxidase and the peroxidase action of cytochrome P-450. Biotransformation catalyzed by the monoxygenase and oxidase action of cytochrome P-450 was affected by cimetidine (probably via its ligand interaction with cytochrome P-450), whereas metabolism by the peroxidase mode of action of cytochrome P-450 was hardly influenced. Ranitidine and famotidine (both pharmacodynamically more potent than cimetidine) only slightly affected cytochrome P-450 activities.
Bast
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Department of Pharmacochemistry, Faculty of Chemistry, Vrije Universiteit, Amsterdam, The Netherlands.
Smid
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K
Timmerman
H
H
D000818:Animals; D001665:Binding Sites; D002927:Cimetidine / Q000378:metabolism / Q000494:pharmacology; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D015738:Famotidine; D006635:Histamine H2 Antagonists / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D011899:Ranitidine / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013844:Thiazoles / Q000378:metabolism / Q000494:pharmacology
D006635:Histamine H2 Antagonists; D013844:Thiazoles; D015738:Famotidine; D002927:Cimetidine; D011899:Ranitidine; D003577:Cytochrome P-450 Enzyme System