Guenette S A, Beaudry F, Marier J F, Vachon P
Department of Veterinary Biomedicine, Faculty of Veterinary Medicine, University of Montreal, St Hyacinthe, Canada.
J Vet Pharmacol Ther. 2006 Aug;29(4):265-70. doi: 10.1111/j.1365-2885.2006.00740.x.
Eugenol, the principle chemical constituent of clove oil, has recently been evaluated for its anesthetic and analgesic properties in fish and amphibians. The objective of this study was to determine the pharmacokinetic (PK) and anesthetic activity of eugenol in rats. Male Sprague-Dawley rats received single i.v. doses of eugenol (0, 5, 10, 20, 40 and 60 mg/kg) and anesthetic level was evaluated with the withdrawal reflex. For the 20 mg/kg dose level, blood and urinary samples were collected over 1 h for the PK assessment. Plasma and blood concentrations of eugenol, as well as metabolite identification in urine, were determined using a novel dansyl chloride derivatization method with liquid chromatography mass spectrometry (LC/MS/MS). PK parameters were calculated using noncompartmental methods. Eugenol-induced loss of consciousness in a dose-dependent manner, with mean (+/-SEM) recovery in reflex time of 167 +/- 42 sec observed at the highest dose level. Mean systemic clearance (Cl) in plasma and blood were 157 and 204 mL/min/kg, respectively. Glucuronide and sulfate conjugates were identified in urine. Overall, eugenol produced a reversible, dose-dependent anesthesia in male Sprague-Dawley rats.
丁香酚是丁香油的主要化学成分，最近已对其在鱼类和两栖动物中的麻醉和镇痛特性进行了评估。本研究的目的是确定丁香酚在大鼠体内的药代动力学（PK）和麻醉活性。雄性Sprague-Dawley大鼠接受单次静脉注射丁香酚（0、5、10、20、40和60 mg/kg），并通过退缩反射评估麻醉水平。对于20 mg/kg剂量水平，在1小时内采集血液和尿液样本进行PK评估。使用新型丹磺酰氯衍生化方法结合液相色谱质谱联用仪（LC/MS/MS）测定血浆和血液中丁香酚的浓度以及尿液中的代谢物鉴定。使用非房室方法计算PK参数。丁香酚以剂量依赖性方式导致意识丧失，在最高剂量水平观察到平均（+/-SEM）反射恢复时间为167 +/- 42秒。血浆和血液中的平均全身清除率（Cl）分别为157和204 mL/min/kg。在尿液中鉴定出葡萄糖醛酸和硫酸盐结合物。总体而言，丁香酚在雄性Sprague-Dawley大鼠中产生了可逆的、剂量依赖性的麻醉作用。
