Urinary Metabolites of p-Hydroxyamphetamine in Man, Rat and Guinea-pig

Abstract

1. The metabolism of (±)-p-hydroxy[¹⁴C]amphetamine has been studied in the rat, guinea-pig and man.

2. Most of the administered ¹⁴C was excreted in the urine within the first 24 h (64–92%), and was present mainly as free and conjugated p-hydroxy[¹⁴C]-amphetamine. In the female rat and female guinea-pig the conjugate was a glucuronide, but in man, who received a much smaller dose, the conjugate was a sulphate ester. A sex difference in conjugation was found in the rat, the female partly conjugating the drug but not the male.

3. Small quantities (1–6% of dose) of p-hydroxynorephedrine, a putative false neurotransmitter, were found in the urine of the three species.

4. Some oxidative degradation of the side chain of p-hydroxyamphetamine occurred in rat and guinea-pig since small amounts of p-hydroxybenzoic acid (1–3%) were detected in the urine.