1. Urinary metabolites of the male Wistar rat dosed i.p. and orally wi
th phentermine (Ph), N-hydroxyphentermine (N-hydroxy-Ph) and p-hydroxy
phentermine (p-hydroxy-Ph) were examined by g.l.c. and g.l.c.-mass spe
ctroscopy. 2. N-hydroxy-Ph which accounted for about 3% dose was ident
ified in the urine of rat dosed i.p. and orally with Ph. The major uri
nary metabolite of Ph dosed i.p. and orally was a p-hydroxy-Ph conjuga
te (51% dose). 3. The major urinary metabolite of N-hydroxy-Ph dosed i
.p. and orally was a p-hydroxy-Ph conjugate (40% dose). A N-hydroxy-Ph
conjugate (12% dose) was identified following i.p. administration of
N-hydroxy-Ph, but was not detected following oral administration. Smal
l amounts of Ph (< 10% dose) and p-hydroxy-Ph (3% dose) were also iden
tified after i.p. and oral administration of N-hydroxy-Ph. 4. The only
urinary metabolite of p-hydroxy-Ph after either i.p. or oral dosing w
as a p-hydroxy-Ph conjugate (65% dose). 5. These results indicate that
N-hydroxy-Ph is a urinary metabolite of Ph in rat; p-hydroxy-Ph is pr
oduced by the hydroxylation of Ph itself and partly by the hydroxylati
on of Ph formed from N-hydroxy-Ph; the p-hydroxy-Ph conjugate is the m
ajor and final metabolite of Ph dosed i.p. and orally.