Identification of two major biliary metabolites of carvedilol in rats

Abstract

1. After separate administration of R(+)-carvedilol, S(-)-carvedilol and (±)-¹⁴C-carvedilol to rats at an oral dose of 10mg/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.