The comparative metabolism and disposition of penfluridol-3H in the rat, rabbit, dog, and man.

ABSTRACT

Penfluridol, 1-[4,4-bis(4-fluorophenyl)butyl]-4-[4-chloro-3-(trifluoromethyl)phenyl]-4-piperidinol, was well absorbed by the rat, rabbit, dog, and man after single oral doses of drug in solution. Penfluridol and its metabolites were widely distributed in tissues of male rats and cleared slowly. The terminal plasma t 1/2 for penfluridol was greater than 40 hr for the rabbit, 227 hr for the dog, and 199 hr for man. Fecal excretion of total radioactivity predominated in the rat, rabbit, and dog whereas in man excretion was evenly divided between urine and feces. The major biotransformation pathways of penfluridol in the rat, rabbit, dog, and man were oxidative N-dealkylation followed by beta-oxidation, conjugation of penfluridol, and conjugation of the acidic metabolites.