Isolation and identification of the new metabolites of 1-[bis(4-fluorophenyl)-methyl]-4-(2,3,4-trimethoxybenzyl)piperazine dihydrochloride (KB-2796) from rat bile, urine and feces.
The metabolites of 1-[bis(4-fluorophenyl)methyl]-4-(2,3,4-trimethoxybenzyl)piperazine dihydrochloride (KB-2796) in the bile, urine and feces in rats were investigated after oral administration of [methine-14C], [benzyl-14C] and unlabelled KB-2796. Their structures were characterized by thin-layer chromatography, mass spectrometry, proton nuclear magnetic resonance and comparison with synthesized authentic compounds. The main pathways of biotransformation of KB-2796 in rats were: (a) O-demethylation at each methoxy group of the trimethoxybenzyl moiety, (b) N-dealkylation at 1 and 4-position of the piperazine ring and (c) hydroxylation at 5-position of the 2,3,4-trimethoxyphenyl ring.
Kawashima
T
T
Product Research and Development Laboratories, Pharmaceuticals Research Center, Kanebo, Ltd., Osaka, Japan.
Satomi
O
O
Awata
N
N
D000818:Animals; D001345:Autoradiography; D001646:Bile / Q000737:chemistry / Q000378:metabolism*; D001711:Biotransformation; D002121:Calcium Channel Blockers / Q000378:metabolism / Q000493:pharmacokinetics* / Q000652:urine; D002852:Chromatography, Ion Exchange; D002855:Chromatography, Thin Layer; D005243:Feces / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D013058:Mass Spectrometry; D010879:Piperazines / Q000378:metabolism / Q000493:pharmacokinetics* / Q000652:urine; D051381:Rats; D011919:Rats, Inbred Strains
D002121:Calcium Channel Blockers; D010879:Piperazines; C052424:lomerizine