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Pharmacokinetics and pharmacodynamics of butorphanol in llamas after intravenous and intramuscular administration

Gwendolyn L. Carroll DVM, DACVA1, Dawn M. Boothe DVM, PhD, DACVIM, DACVCP2, Sandee M. Hartsfield DVM, MS, DACVA3, Elizabeth A. Martinez DVM, DACVA4, Angela C. Spann BS5, and Adrian Hernandez6
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  • 1 Departments of Small Animal Medicine and Surgery, College of Veterinary Medicine, Texas A&M University, College Station, TX 77843-4474.
  • | 2 Departments of Physiology and Pharmacology, College of Veterinary Medicine, Texas A&M University, College Station, TX 77843-4474.
  • | 3 Departments of Small Animal Medicine and Surgery, College of Veterinary Medicine, Texas A&M University, College Station, TX 77843-4474.
  • | 4 Departments of Small Animal Medicine and Surgery, College of Veterinary Medicine, Texas A&M University, College Station, TX 77843-4474.
  • | 5 Departments of Small Animal Medicine and Surgery, College of Veterinary Medicine, Texas A&M University, College Station, TX 77843-4474.
  • | 6 Departments of Small Animal Medicine and Surgery, College of Veterinary Medicine, Texas A&M University, College Station, TX 77843-4474.

Abstract

Objective—To evaluate disposition of butorphanol after IV and IM administration, effects on physiologic variables, and analgesic efficacy after IM administration in llamas.

Design—Nonrandomized crossover study.

Animals—6 healthy adult male llamas.

Procedure—Butorphanol (0.1 mg/kg [0.045 mg/lb] of body weight) was administered IM first and IV 1 month later. Blood samples were collected intermittently for 24 hours after administration. Plasma butorphanol versus time curves were subjected to pharmacokinetic analysis. Two months later, butorphanol (0.1 mg/kg) was administered IM, and physiologic variables and analgesia were assessed.

Results—Extrapolated peak plasma concentrations after IV and IM administration were 94.8 ± 53.1 and 34.3 ± 11.6 ng/ml, respectively. Volume of distribution at steady state after IV administration was 0.822 ± 0.329 L/kg per minute and systemic clearance was 0.050 ± 0.014 L/kg per minute. Slope of the elimination phase was significantly different, and elimination half-life was significantly shorter after IV (15.9 ± 9.1 minutes) versus IM (66.8 ± 13.5 minutes) administration. Bioavailability was 110 ± 49% after IM administration. Heart rate decreased and rectal temperature increased. Somatic analgesia was increased for various periods. Two llamas became transiently sedated, and 2 became transiently excited after butorphanol administration.

Conclusions and Clinical Relevance—Although IV administration of butorphanol results in a short halflife that may limit its analgesic usefulness, the elimination half-life of butorphanol administered IM is likely to be clinically useful. The relationship among plasma butorphanol concentration, time, and analgesia differed with the somatic analgesia model; clinically useful analgesia may occur at lower plasma concentrations than those reported here. (J Am Vet Med Assoc 2001;219:1263–1267)

Abstract

Objective—To evaluate disposition of butorphanol after IV and IM administration, effects on physiologic variables, and analgesic efficacy after IM administration in llamas.

Design—Nonrandomized crossover study.

Animals—6 healthy adult male llamas.

Procedure—Butorphanol (0.1 mg/kg [0.045 mg/lb] of body weight) was administered IM first and IV 1 month later. Blood samples were collected intermittently for 24 hours after administration. Plasma butorphanol versus time curves were subjected to pharmacokinetic analysis. Two months later, butorphanol (0.1 mg/kg) was administered IM, and physiologic variables and analgesia were assessed.

Results—Extrapolated peak plasma concentrations after IV and IM administration were 94.8 ± 53.1 and 34.3 ± 11.6 ng/ml, respectively. Volume of distribution at steady state after IV administration was 0.822 ± 0.329 L/kg per minute and systemic clearance was 0.050 ± 0.014 L/kg per minute. Slope of the elimination phase was significantly different, and elimination half-life was significantly shorter after IV (15.9 ± 9.1 minutes) versus IM (66.8 ± 13.5 minutes) administration. Bioavailability was 110 ± 49% after IM administration. Heart rate decreased and rectal temperature increased. Somatic analgesia was increased for various periods. Two llamas became transiently sedated, and 2 became transiently excited after butorphanol administration.

Conclusions and Clinical Relevance—Although IV administration of butorphanol results in a short halflife that may limit its analgesic usefulness, the elimination half-life of butorphanol administered IM is likely to be clinically useful. The relationship among plasma butorphanol concentration, time, and analgesia differed with the somatic analgesia model; clinically useful analgesia may occur at lower plasma concentrations than those reported here. (J Am Vet Med Assoc 2001;219:1263–1267)