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

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.