In vivo and in vitro assessment of mirtazapine pharmacokinetics in cats with liver disease

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