Carroll Gwendolyn L, Boothe Dawn M, Hartsfield Sandee M, Waller Mandy K, Geller Sue C
Department of Veterinary Small Animal Medicine and Surgery, Texas A & M University, College Station, TX, USA.
Department of Veterinary Physiology and Pharmacology, Texas A & M University, College Station, TX, USA.
Vet Anaesth Analg. 2001 Oct;28(4):188-195. doi: 10.1046/j.1467-2987.2001.00071.x. Epub 2016 Nov 15.
To evaluate disposition of a single dose of butorphanol in goats after intravenous (IV) and intramuscular (IM) administration and to relate behavioral changes after butorphanol administration with plasma concentrations.
Randomized experimental study.
Six healthy 3-year-old neutered goats (one male and five female) weighing 46.5 ± 10.5 kg (mean ± D).
Goats were given IV and IM butorphanol (0.1 mg kg) using a randomized cross-over design with a 1-week interval between treatments. Heparinized blood samples were collected at fixed intervals for subsequent determination of plasma butorphanol concentrations using an enzyme linked immunosorbent assay (ELISA). Pharmacokinetic values (volume of distribution at steady state [Vd], systemic clearance [Cl], extrapolated peak plasma concentration [C] or estimated peak plasma concentration [C], time to estimated peak plasma concentration [T], distribution and elimination half-lives [t], and bioavailability) were calculated. Behavior was subjectively scored. A two-tailed paired t-test was used to compare the elimination half-lives after IV and IM administration. Behavioral scores are reported as median (range). A Friedman Rank Sums test adjusted for ties was used to analyze the behavioral scores. A logit model was used to determine the effect of time and concentration on behavior. A value of p < 0.05 was considered significant.
Volume of distribution at steady state after IV administration of butorphanol was 1.27 ± 0.73 L kg, and Cl was 0.0096 ± 0.0024 L kg minute. Extrapolated C of butorphanol after IV administration was 146.5 ± 49.8 ng mL. Estimated C after IM administration of butorphanol was 54.98 ± 14.60 ng mL, and T was 16.2 ± 5.2 minutes; bioavailability was 82 ± 41%. Elimination half-life of butorphanol was 1.87 ± 1.49 and 2.75 ± 1.93 hours for IV and IM administration, respectively. Goats became hyperactive after butorphanol administration within the first 5 minutes after administration. Behavioral scores for goats were significantly different from baseline at 15 minutes after IV administration and at 15 and 30 minutes after IM administration. Both time and plasma butorphanol concentration were predictors of behavior. Behavioral scores of all goats had returned to baseline by 120 minutes after IV administration and by 240 minutes after IM administration. Conclusions and Clinical Relevance The dose of butorphanol (0.1 mg kg, IV or IM) being used clinically to treat postoperative pain in goats has an elimination half-life of 1.87 and 2.75 hours, respectively. Nonpainful goats become transiently excited after IV and IM administration of butorphanol. Clinical trials to validate the efficacy of butorphanol as an analgesic in goats are needed.
评估静脉注射（IV）和肌肉注射（IM）单剂量布托啡诺后在山羊体内的处置情况，并将布托啡诺给药后的行为变化与血浆浓度相关联。
随机实验研究。
6只健康的3岁去势山羊（1只雄性和5只雌性），体重46.5±10.5千克（平均值±标准差）。
采用随机交叉设计，在两次治疗之间间隔1周，给山羊静脉注射和肌肉注射布托啡诺（0.1毫克/千克）。在固定时间间隔采集肝素化血样，随后使用酶联免疫吸附测定法（ELISA）测定血浆布托啡诺浓度。计算药代动力学值（稳态分布容积[Vd]、全身清除率[Cl]、外推峰血浆浓度[Cmax]或估计峰血浆浓度[C]、达到估计峰血浆浓度的时间[Tmax]、分布和消除半衰期[t1/2]以及生物利用度）。对行为进行主观评分。采用双尾配对t检验比较静脉注射和肌肉注射后的消除半衰期。行为评分报告为中位数（范围）。采用经 ties 调整的弗里德曼秩和检验分析行为评分。使用逻辑模型确定时间和浓度对行为的影响。p值<0.05被认为具有统计学意义。
静脉注射布托啡诺后的稳态分布容积为1.27±0.73升/千克，Cl为0.0096±0.0024升/千克·分钟。静脉注射布托啡诺后的外推Cmax为146.5±49.8纳克/毫升。肌肉注射布托啡诺后的估计Cmax为54.98±14.60纳克/毫升，Tmax为16.2±5.2分钟；生物利用度为82±41%。布托啡诺的消除半衰期静脉注射和肌肉注射分别为1.87±1.49小时和2.75±1.93小时。给药后前5分钟内，布托啡诺给药后山羊变得多动。静脉注射后15分钟以及肌肉注射后15分钟和30分钟时，山羊的行为评分与基线有显著差异。时间和血浆布托啡诺浓度均为行为的预测因素。静脉注射后120分钟和肌肉注射后240分钟时，所有山羊的行为评分均恢复到基线水平。结论与临床意义 临床上用于治疗山羊术后疼痛的布托啡诺剂量（0.1毫克/千克，静脉注射或肌肉注射）的消除半衰期分别为1.87小时和2.75小时。非疼痛状态的山羊静脉注射和肌肉注射布托啡诺后会出现短暂兴奋。需要进行临床试验以验证布托啡诺作为山羊镇痛药的疗效。
