Pharmacokinetics and pharmacodynamics of a high concentration of buprenorphine (Simbadol) in conscious horses after subcutaneous administration

Abstract Objective To determine the pharmacokinetics and pharmacodynamics of high concentration formulation of buprenorphine (1.8 mg mL−1; Simbadol) following subcutaneous (SC) administration in horses. Study design Prospective, randomized, crossover trial. Animals A total of six healthy adult horses weighing 521–602 kg. Methods On three occasions, Simbadol (0.005 mg kg−1; treatment S5), (0.0025 mg kg−1; treatment S2.5) or saline (treatment SAL) were administered SC at least 7 days apart, in random order. Electrical nociceptive threshold (ENT) measured on the neck region, physiologic variables, locomotor activity, degree of restlessness and presence of excitatory signs were measured at baseline and for up to 48 hours after injection. Blood was collected for pharmacokinetics analysis at the same time intervals and plasma buprenorphine concentration (Cp) measured using liquid chromatography–tandem mass spectrometry. Results Buprenorphine was quantifiable in all horses from 15 minutes after administration up to 8–12 hours. ENT was significantly increased in S2.5 compared with SAL at 0.75–6 hours after treatment. Increase in locomotor activity and compulsive behavior were recorded in all horses after Simbadol, and degree of restlessness was significantly higher than SAL for a sustained time in S5. Gastrointestinal motility significantly decreased in all horses after Simbadol and returned to baseline by 16 hours after treatment. Conclusions and clinical relevance Subcutaneous Simbadol was rapidly absorbed in horses and Cp decreased rapidly. Side effects commonly seen in horses after opioids were observed in both Simbadol treatments, but degree of opioid-induced excitement lasted significantly longer in treatment S5. Simbadol (0.0025 mg kg−1) SC has the potential to be used clinically to treat pain in horses. However, at this dose, duration of antinociceptive effects was not longer than reported for conventional buprenorphine, and side effects, including reduction in gastrointestinal motility and increased locomotor activity, were documented.