Comparative oxidative metabolic profiles of clomipramine in cats, rats and dogs: preliminary results from an in vitro study.
The objectives of this in vitro study were to describe cytochrome-dependent metabolism of clomipramine in canine and feline microsomes, compare metabolic profiles between cats, rats and dogs, and investigate a potential gender-related difference in metabolic activity between male and female cats. Pooled liver microsomes were incubated with clomipramine, where species and gender-specific reactions were initiated by the addition of a nicotinamide adenine dinucleotide phosphate regenerating system and quenched with methanol at 0, 5, 15, 30, 45 and 60 min, and 0, 30, 60, 90, 120, 180, 240 and 360 min respectively. Liquid chromatography tandem mass spectrometry was used to measure clomipramine and its metabolites. Preliminary results showed that cat microsomes biotransformed clomipramine slower and less efficiently than rat and dog microsomes. Moreover, gender differences in metabolic profiles suggested that male cat microsomes may be less efficient demethylators and hydroxylators than female cat microsomes. As gender metabolic differences may carry clinical significance for this antidepressant, further studies are warranted.
Lainesse
C
C
Département de Biomédecine Vétérinaire, Faculté de Médecine Vétérinaire, Université de Montréal, St-Hyacinthe, QC, Canada. chantallainesse@rogers.com
Frank
D
D
Beaudry
F
F
Doucet
M
M
D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D002415:Cats / Q000378:metabolism; D002853:Chromatography, Liquid; D002997:Clomipramine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004285:Dogs / Q000378:metabolism; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D013058:Mass Spectrometry; D008862:Microsomes, Liver / Q000378:metabolism; D010084:Oxidation-Reduction; D051381:Rats / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D013045:Species Specificity