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 (C) and time to C 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.

中文翻译：

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盐酸索他洛尔在健康猫体内的单剂量和多剂量药代动力学

本研究的目的是描述健康猫中索他洛尔的单剂量和多剂量药代动力学以及尿消除情况。在一项为期两周的清除期的随机交叉研究中，六只成年专门饲养的猫以单次静脉推注和单次口服剂量的方式给予猫 2 毫克索他洛尔/公斤体重。然后，这些猫每 12 小时口服 3 毫克索他洛尔/公斤，持续两周。在给药后 48 小时内的预定时间点收集血样，使用超高压液相色谱和质谱法对索他洛尔进行定量。使用非房室分析来获得药代动力学参数。数据以中位数（最小–最大）表示。静脉注射后，血浆清除率和分布容积分别为9.22 mL/min/kg (5.69–10.89 mL/min/kg)和2175.56 mL/kg (1961–2341.57 mL/kg)。单次口服剂量后的生物利用度为 88.41% (62.75–130.29)。单次口服剂量（2mg/kg）后血浆峰浓度（Cmax）和达到Cmax的时间分别为0.94μg/mL（0.45-1.17μg/mL）和1.5小时（0.5-4小时），以及2.29μg/mL（慢性口服给药（3mg/kg）分别为1.91-2.48μg/mL）和1.0小时（0.5-1.5小时）。单次和长期口服给药的消除半衰期分别为 2.75 小时（2.52-4.10 小时）和 4.29 小时（3.33-5.53 小时）。长期给药后蓄积指数为1.17（1.09-1.29）。尿索他洛尔回收率为静脉剂量的 81-108%。据报道，口服索他洛尔的血浆浓度对其他物种有效，具有良好至极好的口服生物利用度。尿液排泄似乎是主要的消除途径。重复口服给药后，估计药物蓄积最小。由于非线性动力学的可能性，建议对猫进行更多研究。