[Studies on the metabolism of antiepilepserine in isolated perfused rat liver].
The metabolism of antiepilepserine, 3,4-methylene dioxycinnamyl piperidine, was studied in isolated perfused rat liver. Two metabolites were separated and purified by means of HPLC. They were identified as 3,4-methylene dioxycinnamyl hydroxypiperidine and 4-hydroxy-3-methoxycinnamyl piperidine by UV and MS. The latter was further confirmed by chemical synthesis. The pharmacokinetics of antiepilepserine in isolated perfused liver was also studied. Parameters obtained include a first order elimination constant, k = 0.0157 +/- 0.0043 min-1, and a half-life, t 1/2 = 46.7 +/- 11.9 min, (n = 6). The amount of antiepilepserine lost during the perfusion could not be compensated by the increased amount of metabolites. Antiepilepserine was found to be tightly bound and stored in the liver. This might be one of the explanations of the first pass effect of antiepilepserine after oral administration.
Dong
S N
SN
Bai
F
F
Yang
H J
HJ
Lou
Y Q
YQ
Liang
W S
WS
D000818:Animals; D000927:Anticonvulsants / Q000378:metabolism* / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid; D002934:Cinnamates / Q000378:metabolism; D066298:In Vitro Techniques; D008099:Liver / Q000378:metabolism*; D010477:Perfusion; D010880:Piperidines / Q000378:metabolism* / Q000493:pharmacokinetics; D051381:Rats
D000927:Anticonvulsants; D002934:Cinnamates; D010880:Piperidines; C061616:3,4-methylenedioxycinnamylhydroxypiperidine; C061617:4-hydroxy-3-methoxycinnamylpiperidine; C037547:ilepcimide