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

• Published in: Journal of veterinary cardiology 2024-02, Vol.51, p.86-96
• Main Authors: Salmon, S.J., Coleman, A.E., Lynn, C.R., Sanders, J.E., Messenger, K.M.
• Format: Article
• Language: English
• Subjects: Administration, Oral; adults; Animals; Antiarrhythmic; Beta-adrenergic blocker; bioavailability; Biological Availability; blood; body weight; Cats; Chromatography, High Pressure Liquid - veterinary; Cross-Over Studies; drugs; excretion; Feline; Half-Life; Infusions, Intravenous - veterinary; intravenous injection; liquid chromatography; mass spectrometry; oral administration; pharmacokinetics; Potassium-channel blocker; Sotalol; species; Tachyarrhythmia
• ISSN: 1760-2734; 1875-0834
• DOI: 10.1016/j.jvc.2023.11.015

The objective of this study was to describe the single- and multiple-dose pharmacokinetics and urinary elimination of sotalol in healthy cats. Six adult purpose-bred cats 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). 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. 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.