METABOLISM OF CHLORPHENIRAMINE-3H BY RAT AND DOG

Chlorpheniramine-3H is rapidly and completely absorbed from the gastrointestinal tract of the rat and the dog. About 70-80 per cent of the administered radioactivity contained in a single acute dose is excreted in urine and feces in 4 days with most of the radioactivity being recovered in urine in 24 hr. When rats, but not dogs, are pretreated with nonradioactive chlorpheniramine and then given the labeled compound, the recovery of tritium in urine and feces is essentially complete in 4 days. Maximum radioactivity in blood in both species was observed 30-60 min after oral drug administration and the blood level fell to half its maximum value in 24 hr. Radioactivity was detected in rat tissues 15 min after dosing and reached peak levels in 30-60 min. About 50 per cent of an oral dose of chlorpheniramine-3H is excreted in rat bile in 24 hr. N-dealkylation is a major pathway for the metabolism of chlorpheniramine-3H in both the rat and the dog. Didesmethylchlorpheniramine is the major dealkylated metabolite detected in urine of both species after the doses of chlorpheniramine investigated. Only 1-3 per cent of chlorpheniramine-3H is excreted unchanged in the urine. © 1969.