Pypendop Bruno H, Ahokoivu Hanna, Honkavaara Juhana
Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, CA, USA.
School of Veterinary Medicine, Veterinary Medical Teaching Hospital, University of California, Davis, CA, USA.
J Vet Pharmacol Ther. 2020 Jan;43(1):1-5. doi: 10.1111/jvp.12796. Epub 2019 Jul 18.
Dexmedetomidine is an alpha-2 adrenoceptor agonist, and vatinoxan is an alpha-2 antagonist believed to poorly cross the blood-brain barrier in cats. Dexmedetomidine-vatinoxan combinations are of interest in anesthetized cats because the anesthetic sparing effect of dexmedetomidine may be preserved while vatinoxan attenuates the adverse cardiovascular effects of dexmedetomidine. The aim of this study was to characterize the pharmacokinetics of dexmedetomidine in cats during administration of isoflurane and vatinoxan. Six healthy adult male castrated cats were anesthetized with isoflurane in oxygen. Vatinoxan was administered using a target-controlled infusion system intended to maintain a plasma concentration of 4 µg/ml. Dexmedetomidine, 35 µg/kg was administered intravenously over 5 min. Plasma dexmedetomidine and vatinoxan concentrations were measured at selected time points ranging from prior to 8 hr after dexmedetomidine administration using liquid chromatography/tandem mass spectrometry. Compartment models were fitted to the time-concentration data using nonlinear mixed-effect modeling. A three-compartment model best fitted the data. Typical value (% interindividual variability) for the three-compartment volumes (ml/kg), the metabolic clearance and the two intercompartment distribution clearances (ml min kg ) were 168 (259), 318 (35), 1,425 (18), 12.4 (31), 39.1 (18), and 29.6 (17), respectively. Mean ± standard deviation plasma vatinoxan concentration was 2.6 ± 0.6 µg/ml.
右美托咪定是一种α-2肾上腺素能受体激动剂，而瓦替诺生是一种α-2拮抗剂，据信在猫体内难以穿过血脑屏障。右美托咪定与瓦替诺生的组合对麻醉猫具有吸引力，因为右美托咪定的麻醉增效作用可能得以保留，而瓦替诺生可减轻右美托咪定的不良心血管效应。本研究的目的是描述在异氟烷和瓦替诺生给药期间猫体内右美托咪定的药代动力学特征。六只健康成年雄性去势猫用氧气中的异氟烷麻醉。使用旨在维持血浆浓度为4μg/ml的靶控输注系统给予瓦替诺生。35μg/kg的右美托咪定在5分钟内静脉给药。使用液相色谱/串联质谱法在右美托咪定给药前至给药后8小时的选定时间点测量血浆右美托咪定和瓦替诺生浓度。使用非线性混合效应模型将房室模型拟合到时间-浓度数据。三室模型最适合该数据。三室容积（ml/kg）、代谢清除率和两个室间分布清除率（ml·min·kg）的典型值（%个体间变异性）分别为168（259）、318（35）、1425（18）、12.4（31）、39.1（18）和29.6（17）。血浆瓦替诺生浓度的平均值±标准差为2.6±0.6μg/ml。
