Pharmacokinetics of buprenorphine following constant rate infusion for postoperative analgesia in dogs undergoing ovariectomy.

Abstract

OBJECTIVE:

To investigate the pharmacokinetics of buprenorphine and its main active metabolite, norbuprenorphine, after administration of an intravenous loading dose followed by constant rate infusion (CRI) in dogs.

STUDY DESIGN:

Prospective, clinical study.

ANIMALS:

A total of seven healthy dogs undergoing elective ovariectomy.

METHODS:

Buprenorphine was administered as a loading dose (intravenous bolus of 15 μg kg-1) followed by CRI (2.5 μg kg-1 hour-1 for 6 hours). Moreover, intraoperative analgesia was supplemented by an intramuscular carprofen (4 mg kg-1) injection, administered prior to surgery, and by lidocaine, administrated through subcutaneous infiltration and through a splash on the ovarian vascular pedicle during surgery. Pain and sedation were scored for all animals throughout the 24-hour study period and rescue analgesia was administered when a visual analogue scale score was > 40 mm. Blood samples were collected from a jugular catheter at regular intervals, and plasma concentrations of buprenorphine and norbuprenorphine were determined by a validated liquid chromatography-tandem mass spectrometry method.

RESULTS:

Buprenorphine showed a two-compartment kinetic profile. Maximum concentration was 23.92 ± 8.64 ng mL-1 at 1 minute (maximum time); elimination half-life was 41.87 ± 17.35 minutes; area under the curve was 486.68 ± 125.66 minutes ng-1 mL-1; clearance was 33.61 ± 13.01 mL minute-1 kg-1, and volume of distribution at steady state was 1.77 ± 0.50 L kg-1. In no case was rescue analgesia required. Norbuprenorphine resulted below the lower limit of quantification in almost all samples.

CONCLUSIONS AND CLINICAL RELEVANCE:

The results suggest that a buprenorphine CRI can be a useful tool for providing analgesia in postoperative patients, considering its minor side effects and the advantages of a CRI compared to frequent boluses. The negligible contribution of norbuprenorphine to the therapeutic effect was confirmed.

• Authors: Andrea Barbarossa, Julie Rambaldi, Massimo Giunti, Anna Zaghini, Marco Cunto, Daniele Zambelli, Simond Valgimigli, Francesco Santoro, Noemi Romagnoli
• Journal: Veterinary anaesthesia and analgesia (Vet Anaesth Analg) Vol. 44 Issue 3 Pg. 435-443 (May 2017) ISSN: 1467-2995 [Electronic] United States
• PMID: 28416162 (Publication Type: Clinical Study, Journal Article)
• Copyright: Copyright © 2017 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.

Chemical References

• Analgesics, Opioid
• Carbazoles
• Buprenorphine
• carprofen

Topics

• Analgesia (veterinary)
• Analgesics, Opioid (administration & dosage, pharmacokinetics)
• Animals
• Buprenorphine (administration & dosage, pharmacokinetics)
• Carbazoles (administration & dosage)
• Dogs
• Female
• Ovariectomy (veterinary)
• Pain Measurement (veterinary)
• Postoperative Period
• Prospective Studies
• Time Factors