Identification of two major biliary metabolites of carvedilol in rats.
1. After separate administration of R(+)-carvedilol, S(-)-carvedilol and (+/-)-14C-carvedilol to rats at an oral dose of 10 mg/kg, the metabolic pattern in the bile was studied using h.p.l.c. with radioactivity and u.v. monitoring. 2. Two major metabolites, M-1 and M-2, present in the bile, accounted for 39% and 22% dose, respectively. 3. M-1 and M-2 were characterized as 1-hydroxycarvedilol O-glucuronide and 8-hydroxycarvedilol O-glucuronide, respectively, from FAB-mass spectrometry, 1H-n.m.r. and enzymic hydrolysis. 4. Oral administration of R(+)-carvedilol led to highly selective excretion of M-1 in bile whereas S(-)-carvedilol resulted predominantly in excretion of M-2 rather than M-1.
Fujimaki
M
M
Drug Metabolism and Analytical Chemistry Research Center, Daiichi Pharmaceutical Co., Ltd., Tokyo, Japan.
Hakusui
H
H
D000284:Administration, Oral; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism; D001646:Bile / Q000378:metabolism; D002227:Carbazoles / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*; D000077261:Carvedilol; D008401:Gas Chromatography-Mass Spectrometry; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D011412:Propanolamines / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013237:Stereoisomerism
D000959:Antihypertensive Agents; D002227:Carbazoles; D011412:Propanolamines; D000077261:Carvedilol