In vivo and in vitro assessment of mirtazapine pharmacokinetics in cats with liver disease.
J Vet Intern Med
; 32(6): 1951-1957, 2018 Nov.
Article
en En
| MEDLINE
| ID: mdl-30307637
ABSTRACT
BACKGROUND:
Liver disease (LD) prolongs mirtazapine half-life in humans, but it is unknown if this occurs in cats with LD and healthy cats. HYPOTHESIS/OBJECTIVES:
To determine pharmacokinetics of administered orally mirtazapine in vivo and in vitro (liver microsomes) in cats with LD and healthy cats. ANIMALS Eleven LD and 11 age-matched control cats.METHODS:
Case-control study. Serum was obtained 1 and 4 hours (22 cats) and 24 hours (14 cats) after oral administration of 1.88 mg mirtazapine. Mirtazapine concentrations were measured by liquid chromatography with tandem mass spectrometry. Drug exposure and half-life were predicted using limited sampling modeling and estimated using noncompartmental methods. in vitro mirtazapine pharmacokinetics were assessed using liver microsomes from 3 LD cats and 4 cats without LD.RESULTS:
There was a significant difference in time to maximum serum concentration between LD cats and control cats (median [range] 4 [1-4] hours versus 1 [1-4] hours; P = .03). The calculated half-life of LD cats was significantly prolonged compared to controls (median [range] 13.8 [7.9-61.4] hours versus 7.4 [6.7-9.1] hours; P < .002). Mirtazapine half-life was correlated with ALT (P = .002; r = .76), ALP (P < .0001; r = .89), and total bilirubin (P = .0008; r = .81). The rate of loss of mirtazapine was significantly different between microsomes of LD cats (-0.0022 min-1 , CI -0.0050 to 0.00054 min-1 ) and cats without LD (0.01849 min-1 , CI -0.025 to -0.012 min-1 ; P = .002). CONCLUSIONS AND CLINICAL IMPORTANCE Cats with LD might require less frequent administration of mirtazapine than normal cats.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Enfermedades de los Gatos
/
Estimulantes del Apetito
/
Mirtazapina
/
Hepatopatías
Tipo de estudio:
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Límite:
Animals
Idioma:
En
Revista:
J Vet Intern Med
Asunto de la revista:
MEDICINA INTERNA
/
MEDICINA VETERINARIA
Año:
2018
Tipo del documento:
Article