Studies on the pharmacokinetics and pharmacodynamics of mirtazapine in healthy young cats

• Published in: Journal of veterinary pharmacology and therapeutics Vol. 34; no. 4; pp. 388 - 396
• Main Authors: QUIMBY, J.M, GUSTAFSON, D.L, SAMBER, B.J, LUNN, K.F
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01-08-2011
• Subjects: Adrenergic alpha-Antagonists - blood; Adrenergic alpha-Antagonists - pharmacokinetics; Adrenergic alpha-Antagonists - pharmacology; Animals; Appetite - drug effects; Appetite Stimulants - blood; Appetite Stimulants - pharmacokinetics; Appetite Stimulants - pharmacology; blood; cats; Cats - metabolism; Chromatography, Liquid - veterinary; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule - veterinary; drugs; Feeding Behavior - drug effects; Female; foods; half life; ingestion; liquid chromatography; Male; mass spectrometry; Mianserin - analogs & derivatives; Mianserin - blood; Mianserin - pharmacokinetics; Mianserin - pharmacology; pharmacokinetics; potassium; Random Allocation; Tandem Mass Spectrometry - veterinary
• DOI: 10.1111/j.1365-2885.2010.01244.x
• EISSN: 1365-2885
• ISSN: 0140-7783

Quimby, J. M., Gustafson, D. L., Samber, B. J., Lunn, K. F. Studies on the pharmacokinetics and pharmacodynamics of mirtazapine in healthy young cats. J. vet. Pharmacol. Therap.34, 388-396. Mirtazapine pharmacokinetics was studied in 10 healthy cats. Blood was collected before, and at intervals up to 72 h after, oral dose of 3.75 mg (high dose: HD) or 1.88 mg (low dose: LD) of mirtazapine. Liquid chromatography coupled to tandem mass spectrometry was used to measure mirtazapine, 8-hydroxymirtazapine and glucuronide metabolite concentrations. Noncompartmental pharmacokinetic modeling was performed. Median half-life was 15.9 h (HD) and 9.2 h (LD). Using Mann-Whitney analysis, a statistically significant difference between the elimination half-life, clearance, area under the curve (AUC) per dose, and AUC∞/dose of the groups was found. Mirtazapine does not appear to display linear pharmacokinetics in cats. There was no significant difference in glucuronidated metabolite concentration between groups. Pharmacodynamics was studied in 14 healthy cats administered placebo, LD and HD mirtazapine orally once in a crossover, blinded trial. In comparison with placebo, cats ingested significantly more food when mirtazapine was administered. No difference in food ingestion was seen between HD and LD, but significantly more behavior changes were seen with the HD. Limited serum sampling during the pharmacodynamic study revealed drug exposure comparable with the pharmacokinetic study, but no correlation between exposure and food consumed. Mirtazapine (LD) was administered daily for 6 days with no drug accumulation detected.