Pharmacokinetics and selected behavioral responses to butorphanol and its metabolites in goats following intravenous and intramuscular administration.
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OBJECTIVE: 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. DESIGN: Randomized experimental study. ANIMALS: Six healthy 3-year-old neutered goats (one male and five female) weighing 46.5 10.5 kg (mean D). METHODS: Goats were given IV and IM butorphanol (0.1 mg kg-1) 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 [VdSS], systemic clearance [ClTB], extrapolated peak plasma concentration [C0] or estimated peak plasma concentration [CMAX], time to estimated peak plasma concentration [TMAX], distribution and elimination half-lives [t1/2], 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. RESULTS: Volume of distribution at steady state after IV administration of butorphanol was 1.27 0.73 L kg-1, and ClTB was 0.0096 0.0024 L kg-1 minute-1. Extrapolated C0 of butorphanol after IV administration was 146.5 49.8 ng mL-1. Estimated CMAX after IM administration of butorphanol was 54.98 14.60 ng mL-1, and TMAX 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-1, 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.
