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J Vet Intern Med. 2011 Sep-Oct;25(5):985-9. doi: 10.1111/j.1939-1676.2011.00780.x. Epub 2011 Aug 30.

The pharmacokinetics of mirtazapine in cats with chronic kidney disease and in age-matched control cats.

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  • 1Department of Clinical Sciences, Colorado State University, Fort Collins, CO, USA. jquimby@colostate.edu

Abstract

BACKGROUND:

Cats with chronic kidney disease (CKD) often experience inappetence, and may benefit from administration of mirtazapine, an appetite stimulant. The pharmacokinetics of mirtazapine in CKD cats is unknown.

HYPOTHESIS:

CKD delays the clearance/bioavailability (CL/F) of mirtazapine.

ANIMALS:

Six CKD cats and 6 age-matched controls (AMC) were enrolled. Two CKD cats each from International Renal Interest Society (IRIS) stage II, III and IV were included.

METHODS:

Blood samples were collected before and 0.5, 1, 1.5, 2, 4, 8, 24, and 48 hours after a single PO dose of 1.88 mg of mirtazapine. Mirtazapine concentrations were measured by liquid chromatography coupled to tandem mass spectrometry. Non-compartmental pharmacokinetic modeling was performed.

RESULTS:

Mean age was 11 years (CKD cats) and 10.8 years (AMC cats). Mean serum creatinine concentration ± standard deviation (SD) was 3.8 ± 1.6 mg/dL (CKD) and 1.3 ± 0.4 mg/dL (AMC). Mean half-life ± SD was 15.2 ± 4.2 hours (CKD) and 12.1 ± 1.1 hours (AMC). Mean area under the curve (AUC) ± SD was 770.6 ± 225.5 ng/mL•hr (CKD) and 555.5 ± 175.4 ng/mL•hr (AMC). Mean CL/F ± SD was 0.6 ± 0.1 L/hr/kg (CKD) and 0.8 ± 0.16 L/hr/kg (AMC). A Mann-Whitney test indicated statistically significant differences in AUC (P = 0.01) and CL/F (P = 0.04) between groups. Calculated accumulation factor for 48-hour dosing in CKD cats was 1.15.

CONCLUSION:

CKD may delay the CL/F of mirtazapine. A single low dose of mirtazapine resulted in a half-life compatible with a 48-hour dosing interval in CKD cats.

Copyright © 2011 by the American College of Veterinary Internal Medicine.

PMID:
21985134
[PubMed - indexed for MEDLINE]
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