Preliminary Pharmacokinetics of Single-Dose Intramuscular Butorphanol in Elephant Seals (Mirounga angustirostris)
1Environmental Medicine Consortium, North Carolina State University, Raleigh, NC, USA; 2Department of Companion Animal and Special Species Medicine, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, USA; 3The Marine Mammal Center, Marin Headlands, Golden Gate National Recreation Area, Sausalito, CA, USA; 4Department of Anatomy, Physiology, and Radiology, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, USA
The Marine Mammal Center (TMMC) in Sausalito, CA, USA is a rehabilitation facility for marine mammals which strand along the central and northern California coast. Animals presented to TMMC have a wide variety of injuries and diseases,1 many of which require pain management. Butorphanol tartrate (Torbugesic®, Fort Dodge Animal Health, Overland Park, KS, USA), a synthetic opioid analgesic with mixed agonist-antagonist activity, is approximately five times more potent than morphine and until recently was not listed as a controlled drug.2 While it is commonly used as an analgesic at TMMC, pharmacokinetic values in marine mammals have not been established. Extrapolation of doses used in domestic animals may not be appropriate in marine mammals, where regional differences in blood flow at common injection sites might significantly affect drug absorption.3 This pilot study was conducted to determine the pharmacokinetics of single-dose intramuscularly administered butorphanol in elephant seals, one of the major species handled at TMMC.1 Four weaned elephant seal pups (mean weight = 66±28 kg) held at TMMC were included in this study. To facilitate repeated blood collection and minimize the stress associated with multiple restraints, a 19-g, 36-inch epidural catheter (Encapsulon, Teleflex, Inc., Duluth, GA, USA) was placed in the dorsal intravertebral vein of each subject. Seals received 0.055 mg/kg of butorphanol by intramuscular injection in the right shoulder. Blood samples were collected at 0, 5, 15, 30, and 45 minutes, and 1, 1.25, 1.5, 2, 3, 4, 5, and 6 hours post-injection of the drug. Blood plasma butorphanol concentrations were analyzed by high-performance liquid chromatography using a reverse-phase C-18 column (Supelco C-18, model 088498AD, Supelco, Bellefonte, PA, USA) and electrochemical detection at 900 mV (LC-4B, Bioanalytical Systems, West Lafayette, IN, USA). Plasma butorphanol concentrations were quantitated using nalorphine (Alltech Applied Sciences Laboratories, State College, PA, USA) as an internal standard. Butorphanol was absorbed rapidly with mean peak plasma concentrations of 241 ng/ml (range: 87–635 ng/ml) occurring at the first time point, 5 minutes post-injection. Plasma butorphanol concentrations could still be detected up to 5 hours post-injection. No adverse reactions were observed in any seals, however, they were subjectively sedated for up to 3 hours post-injection.
The authors thank Dr. Frances Gulland, Tracey Goldstein, Diane Paschall, and Deb Wickham at TMMC for assistance with sample collection and preparation. We also thank Susan Lankford for her contributions to the laboratory analysis.
1. Gerber, J.A., J. Roletto, L.E. Morgan, D.M. Smith, and L.J. Gage. 1993. Findings in pinnipeds stranded along the central and northern California coast, 1984–1990. J Wildl Dis. 29:423–433.
2. Jaffe, J.H., and W.R. Martin. 1985. Opioid analgesics and antagonists. In: The Pharmacological Basis of Therapy. MacMillan Publishing, New York, NY. 523.
3. Evans, E.F., J.D. Proctor, M.J. Fratkin, J. Velandia, and A.J. Wasserman. 1975. Blood flow in muscle groups and drug absorption. Clin Pharmacol Ther. 17:44–47.