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Abstract
1. Excretion of urinary and biliary radioactivity, and metabolites of [3H]mephentermine (MP), after i.p. or subcutaneous administration of [3H]MP to male Wistar rats, were determined by preparative t.l.c.-liquid scintillation counting.
2. About 45% of the radioactivity administered i.p. was excreted in the 24 h urine. The major urinary metabolite was conjugated p-hydroxymephentermine (p-hydroxy-MP), which accounted for about 18% of the administered radioactivity in the 24 h urine.
3. About 4·2% of the radioactivity administered subcutaneously was excreted in bile during 24 h. The major biliary metabolite was conjugated p-hydroxy-MP, which accounted for about 39% of the radioactivity excreted in the bile in 24 h.
4. Urinary and biliary minor metabolites detected were phentermine (Ph), p-hydroxyphentermine (p-hydroxy-Ph), N-hydroxyphentermine (N-hydroxy-Ph), N-hydroxymephentermine (N-hydroxy-MP) and their conjugates, and conjugated MP.
5. The conjugates were considered to be glucuronides from the inhibitory effect of saccharic acid 1,4-lactone on their hydrolysis with β-glucuronidase.
6. Biliary excretion rates of conjugated p-hydroxy-Ph and p-hydroxy-MP reached maxima at 3 to 4h, and non-conjugated metabolites were maximal at 1 to 2h, after administration. 50% of the biliary metabolites was excreted within 5 h.