PT  - JOURNAL ARTICLE
AU  - K. L. HINTZE
AU  - J. S. WOLD
AU  - L. J. FISCHER
TI  - DISPOSITION OF CYPROHEPTADINE IN RATS, MICE, AND HUMANS AND IDENTIFICATION OF A STABLE EPOXIDE METABOLITE
DP  - 1975 Jan 01
TA  - Drug Metabolism and Disposition
PG  - 1--9
VI  - 3
IP  - 1
4099  - http://dmd.aspetjournals.org/content/3/1/1.short
4100  - http://dmd.aspetjournals.org/content/3/1/1.full
SO  - Drug Metab Dispos1975 Jan 01; 3
AB  - Radioactivity was excreted in the urine and feces of rats, mice, and humans after a dose of 14C-cyproheptadine. The major metabolite in rat urine was unconjugated, but the majority of radioactive materials in mouse and human urine were conjugated with glucuronic acid. Identification of the rat urinary metabolite of cyproheptadine as an epoxide was accomplished with mass spectrometry and other methods. The rat metabolite was 10,11-epoxydesmethylcy-proheptadine and accounted for about 25% of a 45-mg dose of cyproheptadine per kg. Only a small amount of this epoxide was found in mouse urine, and none was apparent in the urine of two humans who received 5 mg of the drug. Dihydrodiols, which could arise by epoxide hydrase hydrolysis of possible 10,11-epoxy metabolites, were not found in the urine of any of the species studied. The epoxide found in rat urine appears to be unusually stable to in vivo hydrolysis. Possible implications of these results in the species-selective pancreotoxicity of cyproheptadine in the rat are presented. Copyright © 1975 by The American Society for Pharmacology and Experimental Therapeutics