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Pharmacokinetics of buprenorphine following intravenous and buccal administration in cats, and effects on thermal threshold
Author(s) -
Hedges A. R.,
Pypendop B. H.,
ShiloBenjamini Y.,
Stanley S. D.,
Ilkiw J. E.
Publication year - 2014
Publication title -
journal of veterinary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.527
H-Index - 60
eISSN - 1365-2885
pISSN - 0140-7783
DOI - 10.1111/jvp.12084
Subject(s) - buccal administration , buprenorphine , pharmacokinetics , volume of distribution , anesthesia , oral administration , drug administration , pharmacodynamics , half life , chemistry , absorption (acoustics) , medicine , pharmacology , opioid , materials science , receptor , composite material
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) k e0 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).