title: Pharmacokinetics of buprenorphine following intravenous and buccal administration in cats, and effects on thermal threshold.
abstract: This study reports the pharmacokinetics of buprenorphine, following i.v. and buccal administration, and the relationship between buprenorphine concentration and its effect on thermal threshold. Buprenorphine (20 μg/kg) was administered intravenously or buccally to six cats. Thermal threshold was determined, and arterial blood sampled prior to, and at various times up to 24 h following drug administration. Plasma buprenorphine concentration was determined using liquid chromatography/mass spectrometry. Compartment models were fitted to the time-concentration data. Pharmacokinetic/pharmacodynamic models were fitted to the concentration-thermal threshold data. Thermal threshold was significantly higher than baseline 44 min after buccal administration, and 7, 24, and 104 min after i.v. administration. A two- and three-compartment model best fitted the data following buccal and i.v. administration, respectively. Following i.v. administration, mean ± SD volume of distribution at steady-state (L/kg), clearance (mL·min/kg), and terminal half-life (h) were 11.6 ± 8.5, 23.8 ± 3.5, and 9.8 ± 3.5. Following buccal administration, absorption half-life was 23.7 ± 9.1 min, and terminal half-life was 8.9 ± 4.9 h. An effect-compartment model with a simple effect maximum model best predicted the time-course of the effect of buprenorphine on thermal threshold. Median (range) ke0 and EC50 were 0.003 (0.002-0.018)/min and 0.599 (0.073-1.628) ng/mL (i.v.), and 0.017 (0.002-0.023)/min and 0.429 (0.144-0.556) ng/mL (buccal).
authors.affiliation: Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, CA, USA.
authors.forename: A R
authors.initials: AR
authors.lastname: Hedges
authors.forename: B H
authors.initials: BH
authors.lastname: Pypendop
authors.forename: Y
authors.initials: Y
authors.lastname: Shilo-Benjamini
authors.forename: S D
authors.initials: SD
authors.lastname: Stanley
authors.forename: J E
authors.initials: JE
authors.lastname: Ilkiw
mesh_terms: D000278:Administration, Buccal; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*; D000818:Animals; D002047:Buprenorphine / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*; D002415:Cats; D018592:Cross-Over Studies; D006358:Hot Temperature / Q000009:adverse effects*; D007275:Injections, Intravenous; D008297:Male; D010146:Pain / Q000209:etiology / Q000517:prevention & control / Q000662:veterinary
chemical_list: D000701:Analgesics, Opioid; D002047:Buprenorphine