Biotransformation of medetomidine in the rat.
1. The metabolites of a novel alpha 2-adrenoceptor agonist, medetomidine, in rat urine after subcutaneous administration at two dose levels (80 micrograms/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.
Salonen
J S
JS
Farmos Group Ltd, Research Center, Turku, Finland.
Eloranta
M
M
D000818:Animals; D001711:Biotransformation; D002264:Carboxylic Acids / Q000652:urine; D002851:Chromatography, High Pressure Liquid; D005965:Glucuronates / Q000652:urine; D006900:Hydroxylation; D007093:Imidazoles / Q000493:pharmacokinetics* / Q000652:urine; D008099:Liver / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D013058:Mass Spectrometry; D020926:Medetomidine; D015394:Molecular Structure; D051381:Rats; D011919:Rats, Inbred Strains; D014316:Tritium
D002264:Carboxylic Acids; D005965:Glucuronates; D007093:Imidazoles; D014316:Tritium; D020926:Medetomidine