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

Abstract

Background: Despite frequent clinical use, information about the pharmacokinetics (PK), clinical effects, and safety of butorphanol in foals is not available.Objectives: 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.Animals: Six healthy mixed breed pony foals between 3 and 12 days of age were used. Methods: 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.Results: The terminal half-life of butorphanol was 2.1 hours and C 0 was 33.2 AE 12.1 ng/mL after IV injection. For IM injection, C max and T max were 20.1 AE 3.5 ng/mL and 5.9 AE 2.1 minutes, respectively. Bioavailability was 66.1 AE 11.9%. There were minimal effects on vital signs. Foals that received butorphanol spent significantly more time nursing than control foals and appeared sedated.Conclusions and Clinical Importance: 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.

Disposition, behavioural and physiological effects of escalating doses of intravenously administered fentanyl to young foals

“…Progressive increases in spontaneous motor activity have been reported in mature horses at doses ranging from 2.5-40 μg/kg bwt [1,12]. The discrepancy in behavioural effects between foals and mature horses at the low fentanyl doses studied here is similar to that reported previously for butorphanol, whereby excitation has been noted in mature horses whereas sedation is observed in foals [13]. administration of doses ≤4 μg/kg bwt of fentanyl to foals elicited a sedative-like effect in most, but not all of animals studied (2/8 at 2 μg/kg bwt; 6/8 [including the 2 from the 2 μg/kg bwt group] at 4 μg/kg bwt).…”

Plasma pharmacokinetics and pharmacodynamics of alfaxalone in neonatal foals after an intravenous bolus of alfaxalone following premedication with butorphanol tartrate

“…This is clinically relevant as cardiac output in the foal is heart rate dependent (Robertson 2005). In contrast, Arguedas et al. (2008) found that butorphanol administered to foals at 0.05 mg kg −1 IV produced no significant changes in heart rate over time whilst at the same time it provided analgesia and sedation.…”

Analgesic effects of butorphanol tartrate and phenylbutazone administered alone and in combination in young horses undergoing routine castration

“…32,33 The pedometer was held in place by use of a light bandage. Pedometerregistered activity was set as the number of steps.…”

“…Thus, for each horse, a gastrointestinal motility score that ranged from 0 to 4 was assigned at each time point. 31,32 Rectal temperature was recorded by use of a digital thermometer. Heart and respiratory rates were determined via auscultation over the left ventral aspect of the thorax and the trachea, respectively.…”