Single- and multiple-dose pharmacokinetics of sotalol hydrochloride in healthy cats.

ABSTRACT

INTRODUCTION/OBJECTIVES: The objective of this study was to describe the single- and multiple-dose pharmacokinetics and urinary elimination of sotalol in healthy cats. ANIMALS Six adult purpose-bred cats MATERIALS AND METHODS: Cats were administered 2 mg sotalol/kg body weight as a single intravenous bolus and as a single oral dose in a randomized crossover study with a two-week washout period. The same cats then received 3 mg sotalol/kg orally every 12 h for two weeks. Blood samples were collected at predetermined time points for 48 h postdose for quantification of sotalol using ultra-high-pressure liquid chromatography with mass spectrometry. Non-compartmental analysis was used to obtain pharmacokinetic parameters. Data are presented as median (min-max). RESULTS: Following intravenous administration, plasma clearance and volume of distribution were 9.22 mL/min/kg (5.69-10.89 mL/min/kg) and 2175.56 mL/kg (1961-2341.57 mL/kg), respectively. Bioavailability was 88.41% (62.75-130.29) following a single oral dose. Peak plasma concentration (Cmax) and time to Cmax were 0.94 µg/mL (0.45-1.17 µg/mL) and 1.5 h (0.5-4 h) after a single oral dose (2 mg/kg), and 2.29 µg/mL (1.91-2.48 µg/mL) and 1.0 h (0.5-1.5 h) with chronic oral dosing (3 mg/kg), respectively. Elimination half-life was 2.75 h (2.52-4.10 h) and 4.29 h (3.33-5.53 h) for single and chronic oral dosing, respectively. Accumulation index was 1.17 (1.09-1.29) after chronic dosing. Urinary sotalol recovery was 81-108% of the intravenous dose. CONCLUSIONS: Oral sotalol administration resulted in plasma concentrations reportedly efficacious in other species, with good to excellent oral bioavailability. Urinary excretion appears to be a major route of elimination. Following repeated oral dosing, minimal drug accumulation was estimated. Additional studies in cats are recommended due to the possibility of nonlinear kinetics.