THE COMPARATIVE METABOLISM OF d-AMPHETAMINE-C14 IN THE RAT, DOG AND MONKEY

Utilizing a carbon 14 tag on the α-position of the side chain, the metabolic fate and quantification of the urinary metabolites of d -amphetamine sulfate has been studied in the rat, dog and squirrel monkey after oral and intraperitoneal dosing regimens. Small differences in urinary excretion rate were observed between the dosage regimens. Urine aliquots were subjected to descending paper chromatography on Whatman No. 1 strips, using a development system of formic acid, isoamyl alcohol, tert. -amyl alcohol and water (2:5:5:10). Liquid scintillation counting was used to determine the radioactivity of 1-cm segments. The percentage of each metabolite was calculated from the plotted histograms. Three metabolites plus the unchanged parent drug were detected in the urine of the treated animals. The metabolites identified were p -hydroxy-amphetamine, its glucuronide conjugate and hippuric acid. The distribution pattern of d -amphetamine-C 14 indicates that the rat metabolizes the drug primarily through ring hydroxylation, while, in the monkey, oxidative deamination is the primary pathway. The dog is unusual in that either pathway may be utilized. Hippuric acid is the major metabolite found in the urine of the monkey.