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Interactions of the histamine H2-receptor antagonist etintidine with rat liver cytochrome P-450: a comparison with cimetidine.

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1
Institut für Rechtsmedizin, Universität Hamburg, Universität-Krankenhaus Eppendorf, Federal Republic of Germany.

Abstract

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.

PMID:
2893298
DOI:
10.1007/bf00164882
[Indexed for MEDLINE]

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