The metabolic fate of amphetamine in man and other species.
1. The fate of [(14)C]amphetamine in man, rhesus monkey, greyhound, rat, rabbit, mouse and guinea pig has been studied. 2. In three men receiving orally 5mg each (about 0.07mg/kg), about 90% of the (14)C was excreted in the urine in 3-4 days. About 60-65% of the (14)C was excreted in 1 day, 30% as unchanged drug, 21% as total benzoic acid and 3% as 4-hydroxyamphetamine. 3. In two rhesus monkeys (dose 0.66mg/kg), the metabolites excreted in 24h were similar to those in man except that there was little 4-hydroxyamphetamine. 4. In greyhounds receiving 5mg/kg intraperitoneally the metabolites were similar in amount to those in man. 5. Rabbits receiving 10mg/kg orally differed from all other species. They excreted little unchanged amphetamine (4% of dose) and 4-hydroxyamphetamine (6%). They excreted in 24h mainly benzoic acid (total 25%), an acid-labile precursor of 1-phenylpropan-2-one (benzyl methyl ketone) (22%) and conjugated 1-phenylpropan-2-ol (benzylmethylcarbinol) (7%). 6. Rats receiving 10mg/kg orally also differed from other species. The main metabolite (60% of dose) was conjugated 4-hydroxyamphetamine. Minor metabolites were amphetamine (13%), N-acetylamphetamine (2%), norephedrine (0.3%) and 4-hydroxynorephedrine (0.3%). 7. The guinea pig receiving 5mg/kg excreted only benzoic acid and its conjugates (62%) and amphetamine (22%). 8. The mouse receiving 10mg/kg excreted amphetamine (33%), 4-hydroxyamphetamine (14%) and benzoic acid and its conjugates (31%). 9. Experiments on the precursor of 1-phenylpropan-2-one occurring in rabbit urine suggest that it might be the enol sulphate of the ketone. A very small amount of the ketone (1-3%) was also found in human and greyhound urine after acid hydrolysis.
D000433:1-Propanol / Q000652:urine; D000661:Amphetamine / Q000378:metabolism* / Q000652:urine; D000818:Animals; D001565:Benzoates / Q000652:urine; D001993:Bronchodilator Agents / Q000652:urine; D002247:Carbon Isotopes; D002854:Chromatography, Paper; D004285:Dogs; D005260:Female; D006168:Guinea Pigs; D000882:Haplorhini; D006626:Hippurates / Q000652:urine; D006801:Humans; D008297:Male; D051379:Mice; D010627:Phenethylamines / Q000652:urine; D011817:Rabbits; D051381:Rats; D013053:Spectrophotometry; D013566:Sympathomimetics / Q000652:urine
D001565:Benzoates; D001993:Bronchodilator Agents; D002247:Carbon Isotopes; D006626:Hippurates; D010627:Phenethylamines; D013566:Sympathomimetics; D000433:1-Propanol; D000661:Amphetamine