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

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 t...

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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
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Summary:	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.
Bibliography:	http://dx.doi.org/10.1111/j.1365-2885.2010.01244.x istex:71652A0CCFDB3A49DA763F610621BBAE30AF76D2 ArticleID:JVP1244 ark:/67375/WNG-7FQV53LH-0 ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23
ISSN:	0140-7783 1365-2885
DOI:	10.1111/j.1365-2885.2010.01244.x