Department of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI 53726-4089, USA.
Psychopharmacology (Berl). 2011 Aug;216(4):511-23. doi: 10.1007/s00213-011-2239-y. Epub 2011 Mar 15.
This study aims to evaluate the pharmacokinetic, behavioral, and motor effects of a liposomal preparation of hydromorphone hydrochloride (LE-hydro) in rhesus monkeys. We administered either 2 mg/kg of LE-hydro (n = 8) subcutaneous (s.c.) or 0.1 mg/kg of standard pharmaceutical hydromorphone HCl (hydro) preparation either intravenous (i.v.; n = 4) or s.c. (n = 5).
Serial blood samples were drawn after injection and analyzed for serum hydro concentration by liquid chromatography/mass spectrometry. Following s.c. injection of 0.1 mg/kg hydro or 2 mg/kg LE-hydro, behavioral evaluations were conducted in groups of rhesus monkeys (n = 10/group) in the presence of a compatible stimulus animal and motor skills were also evaluated (n = 10/group). The motor skills test consisted of removing a food reward (carrot ring) from either a straight peg (simple task) or a curved peg (difficult task).
LE-hydro (MRT(0-INF) = 105.9 h) demonstrated extended-release pharmacokinetics compared to hydro when administered by either i.v. (MRT(0-INF) =1.1 h) or s.c. (MRT(0-INF) =1.3 h) routes. Hydro did not affect motor performance of the simpler task, but the monkeys' performance deteriorated on the more difficult task at 0.5 and 1 h after injection. LE-hydro had no effect on motor skills in either the simpler or more difficult task.
The results of these studies indicate that LE-hydro has a pharmacokinetic and behavioral side effects profile consistent with an analgesic that could be tested for surgical use in animals. Our studies also expand the use of rhesus monkeys as a translational behavioral pharmacodynamics model for testing extended-release opioid medication.
本研究旨在评估盐酸氢吗啡酮脂质体（LE-羟）在恒河猴中的药代动力学、行为和运动效应。我们分别给 8 只恒河猴皮下（s.c.）注射 2mg/kg 的 LE-羟或 4 只恒河猴静脉（i.v.；n=4）或 5 只恒河猴皮下（s.c.；n=5）注射 0.1mg/kg 的标准药物盐酸氢吗啡酮（hydro）制剂。
注射后采集系列血样，用液质联用分析法测定血清中氢吗啡酮浓度。皮下注射 0.1mg/kg hydro 或 2mg/kg LE-hydro 后，对恒河猴进行行为评估（n=10/组），同时评估运动技能（n=10/组）。运动技能测试包括从直柱（简单任务）或弯柱（困难任务）上取下食物奖励（胡萝卜环）。
与 i.v.（MRT(0-INF)=1.1 h）或 s.c.（MRT(0-INF)=1.3 h）途径相比，LE-hydro（MRT(0-INF)=105.9 h）表现出延长的药代动力学释放。hydro 对简单任务的运动性能没有影响，但在注射后 0.5 和 1 小时，猴子在更困难的任务中的表现恶化。LE-hydro 对简单或更困难的任务中的运动技能均无影响。
这些研究的结果表明，LE-hydro 的药代动力学和行为副作用特征与可用于动物手术的阿片类镇痛药一致。我们的研究还扩展了恒河猴作为一种用于测试延长释放阿片类药物的转化行为药效动力学模型的用途。
