Pharmacokinetics and pharmacodynamics comparison between subcutaneous and intravenous butorphanol administration in horses

Abstract

The study objective was to compare butorphanol pharmacokinetics and physiologic effects following intravenous and subcutaneous administration in horses. Ten adult horses received 0.1 mg/kg butorphanol by either intravenous or subcutaneous injections, in a randomized crossover design. Plasma concentrations of butorphanol were measured at predetermined time points using highly sensitive liquid chromatography-tandem mass spectrometry assay (LC-MS/MS). Demeanor and physiologic variables were recorded. Data were analyzed with multivariate mixed-effect model on ranks (P ≤ 0.05). For subcutaneous injection, absorption half-life and peak plasma concentration of butorphanol were 0.10 ± 0.07 h and 88 ± 37.4 ng/mL (mean ± SD), respectively. Bioavailability was 87%. After intravenous injection, mean ± SD butorphanol steady-state volume of distribution and clearance was 1.2 ± 0.96 L/kg and 0.65 ± 0.20 L/kg/h, respectively. Terminal half-lives for butorphanol were 2.31 ± 1.74 h and 5.29 ± 1.72 h after intravenous and subcutaneous administrations. Subcutaneous butorphanol reached and maintained target plasma concentrations >10 ng/mL for 2 ± 0.87 h (Mean ± SD), with less marked physiologic and behavioral effects compared to intravenous injection. Subcutaneous butorphanol administration is an acceptable alternative to the intravenous route in adult horses.

Synovial butorphanol concentrations and mechanical nociceptive thresholds after intravenous regional limb perfusion in standing sedated horses

“…Sellon et al 20 also evaluated the severity of gastrointestinal and locomotor side effects and found that those, after the constant‐rate infusion, were significantly less severe. A similar pattern of less severe side effects was also reported in association with lower plasma levels achieved after subcutaneous vs IV administration . While it is tempting to try to draw conclusions based on these studies, how these systemic concentrations compare to those required locally is unknown.…”

“…While it could be argued that this short duration limits its use for ongoing management, the concentrations achieved in the surrounding tissues after IVRLP should be considered. The half‐life of butorphanol after subcutaneous administration has been reported to be longer than that after IV administration . The degree of extravascular diffusion during IVRLP may lead to subcutaneous retention, thereby sustaining concentrations in the treated region .…”

“…Butorphanol is another opioid that is more readily available and widely used in equine practice . Its effects after systemic administration in adult horses have been well studied . It is also effective and well‐tolerated in young foals .…”

Influence of caudal epidural analgesia on cortisol concentrations and pain‐related behavioral responses in mares during and after ovariectomy via colpotomy

“…Systemic opioids such as butorphanol have profound analgesic effects but may lead to complications, such as central nervous system excitation, bradycardia, ataxia, and gastrointestinal stasis . In addition, clearance of butorphanol is rapid because it has a half‐life of 2 hours . In contrast, epidural administration of hydrophilic opioids (such as morphine), when accompanied by α‐2 agonists, has a duration of analgesia of up to 24 hours and less systemic absorption, which translates to reduced side effects …”

“…8,9 In addition, clearance of butorphanol is rapid because it has a half-life of 2 hours. 10 In contrast, epidural administration of hydrophilic opioids (such as morphine), when accompanied by a-2 agonists, has a duration of analgesia of up to 24 hours and less systemic absorption, which translates to reduced side effects. 11 The first objective of this study was to evaluate the effect of the addition of caudal epidural detomidine and morphine during ovariectomy via colpotomy versus systemic sedation and analgesia alone during the procedure.…”