Yu Shipeng, Zhang Xiaofeng, Sun Yichun, Peng Yingxu, Johnson James, Mandrell Tim, Shukla Atul J, Laizure S Casey
Department of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Science Center, Memphis, USA.
J Am Assoc Lab Anim Sci. 2006 May;45(3):12-6.
Buprenorphine is a potent partial m-opioid agonist that is used as an analgesic in animals and humans to ameliorate moderate to severe pain and in the treatment of opiate addiction as an alternative to methadone maintenance. The purpose of this study was to characterize the pharmacokinetics of buprenorphine after intravenous administration in mice. Mice (n=48) were given 2.4 mg/kg buprenorphine (HCl salt) by intravenous bolus injection, and groups of 4 mice were euthanized at 5, 15, and 30 min and 1, 2, 3, 5, 7, 9, 12, 18, and 24 h after drug administration. Plasma concentrations of buprenorphine and norbuprenorphine were determined using liquid chromatography-tandem mass spectrometry. By using the mean concentrations at each time point (n=4), pharmacokinetic parameters were estimated for buprenorphine using a 3-compartment model with the reciprocal of the predicted concentration as the weight factor. The estimated values for the exponents of the 1st, 2nd, and terminal compartments; volume of distribution at steady state; clearance; and area under the concentration-time curve were 12.8/h, 2.13/h, 0.239/h, 6.5 l/kg, 4.3 l/h/kg, and 559 microg/lxh, respectively. In addition, we compare the pharmacokinetic disposition of buprenorphine in the mouse with that previously reported for other species.
丁丙诺啡是一种强效的μ-阿片受体部分激动剂，在动物和人类中用作镇痛药，以减轻中度至重度疼痛，并作为美沙酮维持治疗的替代药物用于阿片类药物成瘾的治疗。本研究的目的是表征丁丙诺啡静脉注射后在小鼠体内的药代动力学特征。给小鼠（n = 48）静脉推注2.4 mg/kg丁丙诺啡（盐酸盐），给药后在5、15和30分钟以及1、2、3、5、7、9、12、18和24小时对每组4只小鼠实施安乐死。使用液相色谱-串联质谱法测定血浆中丁丙诺啡和去甲丁丙诺啡的浓度。通过使用每个时间点的平均浓度（n = 4），以预测浓度的倒数作为权重因子，使用三室模型估算丁丙诺啡的药代动力学参数。第一、第二和终末室指数、稳态分布容积、清除率以及浓度-时间曲线下面积的估算值分别为12.8/h、2.13/h、0.239/h、6.5 l/kg、4.3 l/h/kg和559μg/lxh。此外，我们比较了丁丙诺啡在小鼠体内的药代动力学处置与先前报道的其他物种的药代动力学处置情况。
