Biliary metabolites of semotiadil fumarate in the rat.
After oral administration of 14C-semotiadil fumarate to rat, 81.3% of the dosed radioactivity was excreted into the bile. Five major biliary metabolites were detected and characterized as phenolic O-glucuronides by FAB mass spectrometry and 1H-nmr spectrometry. From these results it was concluded that the first step in the metabolism of semotiadil in rat was oxidations at various portions around the molecule to produce phenols. These oxidations implied the ring-opening of the methylenedioxy ring, O-demethylation of the methoxybenzene, hydroxylation of the ring, and aromatic N-demethylation. The next step was O-glucuronidation of the resulting intermediate phenolic metabolites.
Nakaoka
M
M
Developmental Research Laboratories, Daiichi Pharmaceutical Co., Ltd, Tokyo, Japan.
Katoh
K
K
Hakusui
H
H
D000818:Animals; D001646:Bile / Q000378:metabolism*; D001711:Biotransformation; D002121:Calcium Channel Blockers / Q000378:metabolism* / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid; D005965:Glucuronates / Q000737:chemistry / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D015394:Molecular Structure; D010084:Oxidation-Reduction; D051381:Rats; D017208:Rats, Wistar; D016339:Spectrometry, Mass, Fast Atom Bombardment; D013844:Thiazoles / Q000378:metabolism* / Q000493:pharmacokinetics
D002121:Calcium Channel Blockers; D005965:Glucuronates; D013844:Thiazoles; C064356:sesamodil