Pharmacokinetics of buprenorphine after intravenous administration in the mouse.

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.