Biotransformation of medetomidine in the rat

Abstract

1. The metabolites of a novel α₂-adrenoceptor agonist, medetomidine, in rat urine after subcutaneous administration at two dose levels (80 μg/kg or 5 mg/kg), and after incubation with rat liver fractions, were characterized by h.p.l.c., ¹H-n.m.r and mass spectrometry.

2. Hydroxylation of a methyl substituent was the main biotransformation in vitro. Hydroxylation occurred at a rate sufficient for high metabolic clearance.

3. The major urinary metabolites were the glucuronide of hydroxymedetomidine (about 35% of urinary metabolites) and medetomidine carboxylic acid (about 40%).

4. Medetomidine unchanged represented about 1% or 10% of the urinary excretion products, dependent on dose.

5. A metabolic pathway consisting of hydroxylation with subsequent glucuronidation, or further oxidation to carboxylic acid, is suggested.