Pharmacokinetics and analgesic effects of intravenous, intramuscular or subcutaneous buprenorphine in dogs undergoing ovariohysterectomy: A randomized, prospective, masked, clinical trial

Abstract

Background: Buprenorphine is used for canine postoperative pain management. This study aimed to describe the pharmacokinetics and evaluate the analgesic efficacy of buprenorphine (Simbadol, 1.8 mg/mL) administered by different routes in dogs undergoing ovariohysterectomy. Twenty-four dogs were included in a randomized, prospective, masked, clinical trial. Buprenorphine (0.02 mg/kg) was administered intravenously (IV), intramuscularly (IM) or subcutaneously (SC) (n = 8/group) 0.5 h before general anesthesia with propofol-isoflurane. Carprofen (4.4 mg/kg SC) was administered after anesthetic induction and before ovariohysterectomy. Pain was scored using the short-form Glasgow composite pain scale for dogs (SF-GCPS). Dogs were administered morphine (0.25 mg/kg IV) when SF-GCPS scores were ≥ 5/20. Blood sampling was performed up to 720 min after drug administration. Plasma buprenorphine and norbuprenorphine concentrations were analyzed using liquid chromatography mass spectrometry. Pharmacokinetics of buprenorphine was described using a non-compartmental model (PK Solver 2.0). Statistical analysis was performed using linear mixed models and Fisher's exact test (p < 0.05). Results: Pain scores were significantly higher than baseline after IV (0.5-2 h), IM (0.5-3 h) and SC (0.5-4 h) but not among groups. Prevalence of rescue analgesia was significantly higher in SC (7/8 dogs) than IV (2/8) but not different between IV and IM (3/8) or IM and SC. The frequency of rescue analgesia was not significantly different among groups (IV = 2, IM = 5 and SC = 9). Norbuprenorphine was not detected. For IV, IM and SC administration, clearance was 1.29, 1.65 and 1.40 L/hour/kg, volume of distribution was 6.8, 14.2 and 40.1 L/kg, the elimination half-life was 3.7, 5.7, 22 h, and the area under the plasma concentration-time curved extrapolated to infinity was 15.7, 12.4 and 16.4 ng/mL/hour, respectively. Bioavailability for IM and SC was 62.6 and 40%, respectively. Maximum plasma concentrations of buprenorphine were 6.2 and 1.3 ng/mL at 0.14 and 0.33 h after IM and SC administration, respectively. Conclusions: The route of administration influences the analgesic efficacy of buprenorphine in dogs. SC administration of buprenorphine failed to provide clinical analgesia due to erratic drug absorption. At the doses administered, the IV and IM routes are preferred for postoperative analgesia.