Urinary and biliary metabolites of mephentermine in male Wistar rats.
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 beta-glucuronidase. 6. Biliary excretion rates of conjugated p-hydroxy-Ph and p-hydroxy-MP reached maxima at 3 to 4 h, and non-conjugated metabolites were maximal at 1 to 2 h, after administration. 50% of the biliary metabolites was excreted within 5 h.
Mori
M
M
Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, Japan.
Uy
N
N
Sakai
K
K
Inoue
M
M
Miyahara
T
T
Kozuka
H
H
D000818:Animals; D001646:Bile / Q000378:metabolism*; D001711:Biotransformation; D002849:Chromatography, Gas; D005965:Glucuronates / Q000378:metabolism; D007700:Kinetics; D008297:Male; D013058:Mass Spectrometry; D008616:Mephentermine / Q000378:metabolism / Q000493:pharmacokinetics* / Q000652:urine; D011865:Radioisotope Dilution Technique; D051381:Rats; D011919:Rats, Inbred Strains; D014316:Tritium
D005965:Glucuronates; D014316:Tritium; D008616:Mephentermine