Interactions of the histamine H2-receptor antagonist etintidine with rat liver cytochrome P-450: a comparison with cimetidine.
The two imidazole histamine H2-receptor antagonists etintidine and cimetidine interact with the rat liver microsomal cytochrome P-450. From type II spectral changes follows that the affinity of rat liver microsomal preparations for etintidine is about 5 times as high as for cimetidine when comparing both high and low affinity binding sites. After pretreatment with phenobarbital etintidine inhibited benzphetamine N-demethylation competitively (app. Ki: 4.0 mmol/l). Cimetidine inhibited benzphetamine N-demethylation in the same range. After pretreatment with phenobarbital both drugs inhibited the oxidation of benzo(a)pyrene for which etintidine showed a higher inhibitory potency than cimetidine. However, this oxidation could not be inhibited when microsomes of 5,6-benzoflavone pretreated rats were used. After pretreatment with 5,6-benzoflavone only etintidine but not cimetidine inhibited the O-deethylation of ethoxyresorufin competitively (app. Ki: 0.2 mmol/l). Etintidine and cimetidine were metabolized by rat liver microsomes to their corresponding sulphoxides. In conclusion, etintidine may cause mainly the same drug interactions as cimetidine but seems to be a more potent inhibitor.
D000818:Animals; D002927:Cimetidine / Q000378:metabolism / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D006635:Histamine H2 Antagonists / Q000378:metabolism / Q000494:pharmacology*; D007093:Imidazoles / Q000378:metabolism / Q000494:pharmacology*; D066298:In Vitro Techniques; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D010084:Oxidation-Reduction; D051381:Rats; D011919:Rats, Inbred Strains
D006635:Histamine H2 Antagonists; D007093:Imidazoles; D002927:Cimetidine; D003577:Cytochrome P-450 Enzyme System; C036616:etintidine