Gehring R, Coetzee J F, Tarus-Sang J, Apley M D
Department of Clinical Sciences, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66502, USA.
J Vet Pharmacol Ther. 2009 Apr;32(2):124-8. doi: 10.1111/j.1365-2885.2008.01010.x.
The objective of this study was to evaluate the plasma pharmacokinetics of ketamine and its active metabolite norketamine administered intravenously at a dose of 0.1 mg/kg together with xylazine (0.05 mg/kg) to control the pain associated with castration in calves. A two-compartment model with an additional metabolite compartment linked to the central compartment was used to simultaneously describe the time-concentration profiles of both ketamine and its major metabolite norketamine. Parameter values estimated from the time-concentration profiles observed in this study were volume of the central compartment (V(c) = 132.82 +/- 68.23 mL/kg), distribution clearance (CL(D) = 15.49 +/- 2.56 mL/min/kg), volume of the peripheral compartment (V(T) = 257.05 +/- 41.65 mL/kg), ketamine clearance by the formation of the norketamine metabolite (CL(2M) = 8.56 +/- 7.37 mL/kg/min) and ketamine clearance by other routes (CL(o) = 16.41 +/- 3.42 mL/kg/min). Previously published data from rats suggest that the metabolite norketamine contributes to the analgesic effect of ketamine, with a potency that is one-third of the parent drug. An understanding of the time-concentration relationships and the disposition of the parent drug and its metabolite is therefore important for a better understanding of the analgesic potential of ketamine in cattle.
本研究的目的是评估静脉注射剂量为0.1mg/kg的氯胺酮及其活性代谢物去甲氯胺酮与赛拉嗪（0.05mg/kg）联合使用时的血浆药代动力学，以控制犊牛去势相关的疼痛。采用一个带有与中央室相连的额外代谢物室的二室模型，同时描述氯胺酮及其主要代谢物去甲氯胺酮的时间-浓度曲线。根据本研究中观察到的时间-浓度曲线估计的参数值为中央室容积（V(c)=132.82±68.23mL/kg）、分布清除率（CL(D)=15.49±2.56mL/min/kg）、周边室容积（V(T)=257.05±41.65mL/kg）、通过形成去甲氯胺酮代谢物的氯胺酮清除率（CL(2M)=8.56±7.37mL/kg/min）和通过其他途径的氯胺酮清除率（CL(o)=16.41±3.42mL/kg/min）。先前发表的大鼠数据表明，代谢物去甲氯胺酮对氯胺酮的镇痛作用有贡献，其效力为母体药物的三分之一。因此，了解母体药物及其代谢物的时间-浓度关系和处置情况，对于更好地理解氯胺酮在牛中的镇痛潜力很重要。
