Metabolism of mephentermine in male guinea pigs and male mice.

1. Urinary metabolites of mephentermine (MP), after i.p. administration of MP to male Hartley guinea pigs and mice, were identified by g.l.c.-electron impact (EI) mass spectrometry. Excretion of urinary radioactivity, and metabolites of 3H-MP, after i.p. administration, were determined by preparative t.l.c.-liquid scintillation counting. 2. About 27% of the radioactivity administered was excreted in the 24 h urine of guinea pigs, and 36% dose was excreted in 5 days. In mice, about 47% of the radioactivity was excreted in the 24 h urine, and 52% in 5 days. 3. Excretion rates of metabolites detected in the 24 h urine of guinea pigs were phentermine (Ph, 7.8%), a conjugate of N-hydroxyphentermine (N-hydroxy-Ph, 3.6%), p-hydroxyphentermine (p-hydroxy-Ph, 1.0%) and its conjugate (2.9%), and other metabolites (conjugates of MP and Ph, N-hydroxymephentermine (N-hydroxy-MP) and its conjugate, p-hydroxymephentermine (p-hydroxy-MP) and its conjugate, and N-hydroxy-Ph; less than 1.0%). The rates of excretion for mice were Ph (11.7%), conjugates of p-hydroxy-MP (3.1%), Ph (2.7%) and p-hydroxy-Ph (1.6%), and N-hydroxy-Ph (1.2%) and other metabolites (conjugates of MP and N-hydroxy-Ph, N-hydroxy-MP and its conjugate, p-hydroxy-Ph, and p-hydroxy-MP; less than 1.0%). 4. These results indicate that MP administered to mice is metabolized mainly to Ph and p-hydroxy-MP by N-demethylation and p-hydroxylation of the parent compound, and in guinea pigs the primary metabolic reaction of MP is N-demethylation producing Ph.(ABSTRACT TRUNCATED AT 250 WORDS)