Pharmacokinetics of buprenorphine following intravenous and buccal administration in cats, and effects on thermal threshold

Authors

  • A. R. Hedges,

    1. Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, CA, USA
    Search for more papers by this author
  • B. H. Pypendop,

    Corresponding author
    1. Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, CA, USA
    • Bruno Pypendop, VM: SRS University of California, One Shields Avenue, Davis, CA 95616, USA. E-mail: bhpypendop@ucdavis.edu

    Search for more papers by this author
  • Y. Shilo-Benjamini,

    1. Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, CA, USA
    Current affiliation:
    1. Koret School of Veterinary Medicine, Veterinary Teaching Hospital, The Hebrew University of Jerusalem, Jerusalem, Israel
    Search for more papers by this author
  • S. D. Stanley,

    1. California Animal Health and Food Safety Laboratory System, School of Veterinary Medicine, University of California, Davis, CA, USA
    Search for more papers by this author
  • J. E. Ilkiw

    1. Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, CA, USA
    Search for more papers by this author

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).

Ancillary