Comparative N-Demethylation of Antihistaminic Agents possessing Dimethylaminoalkyl Group by Liver Preparations from Four Animal Species

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The N-demethylation of five antihistaminics possessing diemethylaminoalkyl group was compared in in vitro production of formaldehyde by liver 9000 g supernatant fraction from four animal species, rat, mouse, guinea pig and rabbit. Sex difference was observed in only rats but the demethylating activities varied from species to species for a drug and from drug to drug in a species. The high demethylating activities were shown for trimeprazine or diphenhydramine by rats and for fenethazine or chlorpheniramine by rabbits. In adult male rats, castration or SKF 525A reduced the activities and 19-nortestosterone phenylpropionate enhanced the activities without the big change in relative order. Phenobarbital induced the activities of female rat liver in almost same proportion for every drug but 3-methylcholanthrene did not show stimulatory effect. The formaldehyde production from N-oxides was comparatively small and did not show the difference among drugs. No correlation between the lipid solubility and the N-demethylation was found. The significance of investigation of species differences in the drug metabolism was discussed.
公益社団法人日本薬学会の論文
1971-04-25