Urinary excretion of amphetamine and 4'-hydroxyamphetamine by Sprague Dawley and dark Agouti rats

Urinary excretion of amphetamine and 4'-hydroxyamphetamine has been studied in male and female Sprague Dawley (SD) and Dark Agouti (DA) rats. The DA rat is an animal model for the cytochrome P450 (P450) 2D poor metabolizer. Rats were given d-amphetamine sulfate (5 mg/kg, i. p.) and urines were collected at 12 hour intervals for extraction and analysis of the amphetamines by HPLC. There was no significant difference between the sexes of either SD and DA rats in urinary 4'-hydroxyamphetamine and amphetamine excretion, but significant differences were seen between the two strains. The percentage of dose per ml urine recovered as 4'-hydroxyamphetamine from the urine over 24 hours was 11.1 and 9.1 in the SD male and female rats, and 2.3 and 2.5 in DA male and female rats, respectively. The percentage of dose per ml urine recovered as amphetamine was correspondingly lower in the SD male and female rats, 1.1 and 1.0, than that of the DA male and female rats, 5.9 and 5.0. These results support our hypothesis that P450 2D is involved in hepatic 4'-hydroxylation of amphetamine in rats.