Pharmacokinetics of Intravenous and Intramuscular Butorphanol in Asian Elephants (Elephas maximus)
Abstract
Captive Asian elephants (Elephas maximus) are susceptible to lameness resulting from foot and joint pain.1 In the past, opioid analgesics, such as the agonist-antagonist butorphanol, have been used clinically for pain management. However, dosages used in treating elephants were often extrapolated from data in horses, with the risk of administering either a sub-efficacious dose or an overdose, both of which are undesirable.
In this study, six adult captive Asian elephants (five female, one male) were administered butorphanol intravenously (IV) and intramuscularly (IM) in a cross over design. The dose was 0.015 mg/kg for both routes with at least 21 days between administrations. Serial blood samples were collected immediately prior to butorphanol administration and at 5, 10, 20, 40 minutes, and 1, 1.5, 2, 3, 4, 5, 6, 8, 10, and 24 hours after injection. The samples were collected into Li heparin vacutainer tubes and centrifuged to obtain plasma. The plasma was separated into cryovials and frozen at -70°C until analyzed using a validated LC/MS assay with a LOQ of 0.025 ng/ml.
The dosage selected for this pharmacologic study in elephants is within the recommended analgesic butorphanol dose range for horses.2 Following IV administration the median pharmacokinetic values that were calculated include: Vdarea, Vdss, C1p, MRT, and half-life (t½). After IM injection the median Cmax, Tmax, and bioavailability (F) were calculated. The Vd data used for extrapolation from published literature on five domestic mammalian species correlated with the values found for elephants. Thus, Vd may be useful to extrapolate an efficacious dose in Asian elephants. Our preliminary results suggest a dosage of 0.015 mg/kg may provide analgesia without evidence of severe sedation. Further studies are necessary to determine the quality and duration of analgesia from the administration of butorphanol in elephants at this recommended dose.
Literature Cited
1. Mikota, S.K., E. Sargent, and L. Georgeian. 1994. Medical Management of the Elephant. Endura Publishing House.
2. Plumb, D.C. 2005. Plumb’s Veterinary Drug Handbook. Blackwell Publishing, Ames, Iowa. 102–105.