Pharmacokinetics of Butorphanol and Evaluation of Physiologic and Behavioral Effects after Intravenous and Intramuscular Administration to Neonatal Foals

Abstract

Despite frequent clinical use, information about the pharmacokinetics (PK), clinical effects, and safety of butorphanol in foals is not available. The purpose of this study was to determine the PK of butorphanol in neonatal foals after IV and IM administration; to determine whether administration of butorphanol results in physiologic or behavioral changes in neonatal foals; and to describe adverse effects associated with its use in neonatal foals. Six healthy mixed breed pony foals between 3 and 12 days of age were used. In a 3-way crossover design, foals received butorphanol (IV and IM, at 0.05 mg/kg) and IV saline (control group). Butorphanol concentrations were determined by high-performance liquid chromatography and analyzed using a noncompartmental PK model. Physiologic data were obtained at specified intervals after drug administration. Pedometers were used to evaluate locomotor activity. Behavioral data were obtained using a 2-hour real-time video recording. The terminal half-life of butorphanol was 2.1 hours and C0 was 33.2 +/- 12.1 ng/mL after IV injection. For IM injection, Cmax and Tmax were 20.1 +/- 3.5 ng/mL and 5.9 +/- 2.1 minutes, respectively. Bioavailability was 66.1 +/- 11.9%. There were minimal effects on vital signs. Foals that received butorphanol spent significantly more time nursing than control foals and appeared sedated. The disposition of butorphanol in neonatal foals differs from that in adult horses. The main behavioral effects after butorphanol administration to neonatal foals were sedation and increased feeding behavior.