Pharmacokinetics of buprenorphine and its metabolite norbuprenorphine in neutered male cats anesthetized with isoflurane

Abstract

Objective: To characterize the pharmacokinetics of buprenorphine and norbuprenorphine in isoflurane-anesthetized cats.

Study design: Prospective experimental study.

Animals: A group of six healthy adult male neutered cats.

Methods: Cats were anesthetized with isoflurane in oxygen. Catheters were placed in a jugular vein for blood sampling and in a medial saphenous vein for buprenorphine and lactated Ringer's solution administration. Buprenorphine hydrochloride (40 μg kg^-1 over 5 minutes) was administered intravenously. Blood samples were collected before buprenorphine administration and at various times up to 12 hours after administration. Plasma buprenorphine and norbuprenorphine concentrations were measured using liquid chromatography/tandem mass spectrometry. Compartment models were fitted to the time-concentration data using nonlinear mixed effect (population) modeling.

Results: A five-compartment model (three compartments for buprenorphine and two compartments for norbuprenorphine) best fitted the data. Typical value (% interindividual variability) for the three buprenorphine volumes of distribution, and the metabolic clearance to norbuprenorphine, the remaining metabolic clearance and the two distribution clearances were 157 (33), 759 (34) and 1432 (43) mL kg^-1, and 5.3 (33), 16.4 (11), 58.7 (27) and 6.0 (not estimated) mL minute^-1 kg^-1, respectively. Typical values (% interindividual variability) for the two norbuprenorphine volumes of distribution, and the norbuprenorphine metabolic and distribution clearances were 1437 (30) and 8428 (not estimated) mL kg^-1 and 48.4 (68) and 235.9 (not estimated) mL minute^-1 kg^-1, respectively.

Conclusions and clinical relevance: The pharmacokinetics of buprenorphine in isoflurane-anesthetized cats were characterized by a medium clearance.

Keywords: buprenorphine; cats; infusion; opioids; pharmacokinetics.