Objective: To describe the pharmacokinetics of buprenorphine in dogs following administration of a high-concentration formulation of buprenorphine.
Study design: Prospective, randomized, crossover study.
Animals: A total of six healthy male intact Beagle dogs, 9–13 months of age and weighing 10.3 ± 1.4 kg (mean ± standard deviation).
Methods: Dogs were randomized to be administered buprenorphine (0.12 mg kg−1; Simbadol, 1.8 mg mL−1) via the intravenous (lateral saphenous) or subcutaneous (dorsal interscapular) route followed by the alternative route of administration after a 14 day interval. Blood was sampled before administration and at set times up to 72 hours after injection. Plasma buprenorphine concentration was measured using liquid chromatography–tandem mass spectrometry.
Results: A 3-compartment model with zero or biphasic rapid and slow first order input in (intravenous or subcutaneous data, respectively) and first-order elimination from the central compartment best fitted the data. The rapid first order input accounted for 63% of the dosage absorption. Typical values (% interindividual variability) for the three compartment volumes were 900 (33), 2425 (not estimated) and 6360 (28) mL kg−1. The metabolic and two distribution clearances were 25.7 (21), 107.5 (74) and 5.7 (61) mL minute−1 kg−1. The absorption half-life for the fast absorption phase was 8.9 minutes with a 0.7 (103) minute delay. The absorption half-life for the slow absorption phase was 347 minutes with a 226 (42) minutes delay. Median (range) bioavailability calculated from noncompartmental analysis was 143 (80–239) %. Calculated terminal half-life was 963 minutes.
Conclusions and clinical relevance: The high-concentration formulation of buprenorphine administered subcutaneously had a large volume of distribution and a rapid absorption phase followed by slower, delayed absorption. The high estimate of bioavailability should be interpreted with caution as values above 100% are most commonly related to experimental issues. / Master of Science / Opioids are ever-increasingly difficult to obtain for veterinary usage, although there is an FDA-approved and veterinary-specific formulation of buprenorphine (Simbadol) commercially available. Although only approved in cats, it has been used off-label in dogs due to its availability, despite minimal empirical evidence for its usage.
Design: Six male beagle dogs were utilized in a randomized crossover study to evaluate the plasma concentrations of buprenorphine after intravenous and subcutaneous administration.
Methodology: All dogs were anesthetized for central venous catheter placement. Following administration of the dosage (intravenous or subcutaneous), whole blood was sampled at set time points from one minute to three days. Blood was centrifuged and plasma removed for analysis of buprenorphine concentration, allowing pharmacokinetic modeling and creation of time-concentration curves.
Results: Side effects were mild and associated with sedation. Appetite was transiently decreased in multiple dogs. A biphasic absorption model was determined from the subcutaneous data, with a rapid first phase accounting for the majority of absorption and a slower second phase occurring several hours later.
Conclusions: The high-concentration formulation of buprenorphine administered subcutaneously resulted in a long terminal half-life and high estimate of bioavailability, although the latter should be interpreted cautiously.
Relevance: The present study showed that the high-concentration formulation of buprenorphine is absorbed from subcutaneous administration in dogs with mild side effects. Further study is warranted on this formulation in dogs.
| Identifer | oai:union.ndltd.org:VTETD/oai:vtechworks.lib.vt.edu:10919/104431 |
| Date | 28 July 2021 |
| Creators | Hansford, Jeremy Dustin |
| Contributors | Biomedical and Veterinary Sciences, Henao Guerrero, Piedad Natalia, Paranjape, Vaidehi Vinay, Davis, Jennifer Lynn |
| Publisher | Virginia Tech |
| Source Sets | Virginia Tech Theses and Dissertation |
| Detected Language | English |
| Type | Thesis |
| Format | ETD, application/pdf, application/pdf |
| Rights | In Copyright, http://rightsstatements.org/vocab/InC/1.0/ |
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