Pharmacokinetics and Intramuscular Bioavailability of a Single Dose of Butorphanol in Asian Elephants (Elephas maximus)

Abstract

Captive Asian elephants (Elephas maximus) are susceptible to lameness resulting from foot and joint pain, including chronic arthritis. In the past, opioid analgesics, such as butorphanol, have been used clinically for pain management. However, dosages used in treating elephants were often extrapolated from data in horses, with no pharmacokinetic information on the specific agents used in elephant species. In this pharmacokinetic study, six adult captive Asian elephants (5 female, 1 male castrate) were administered a 0.015 mg/kg dose of butorphanol by both i.v. and i.m. routes. A complete crossover design was used with a 3-wk washout period between treatments. Serial blood samples were collected immediately prior to butorphanol administration and at 5, 10, 20, and 40 min and 1, 1.5, 2, 3, 4, 5, 6, 8, 10, and 24 h after administration. The butorphanol analysis was performed using a validated liquid chromatography–mass spectrophotometric assay with a limit of quantitation of 0.025 ng/ml. The mean Cmax after i.m. administration was 7.9 ng/ml, with a corresponding Tmax of 40 min and t½ of 7.1 h. After i.v. administration, the mean Vdss was 1.4 L/kg and the mean Clp was 0.26 L/kg/h. Mean i.m. bioavailability was 37%. The results indicate that butorphanol used at 0.015 mg/kg i.m. or i.v. could be useful in elephants when given for pain control.

Zoo elephant research: contributions to conservation of captive and free‐ranging species

“…Pharmacokinetic studies conducted with NSAIDs in elephants (Table 2) include ibuprofen (Bechert & Christensen, 2007), ketoprofen (Hunter et al, 2003), phenylbutazone (Bechert et al, 2008), and trials with flunixin meglumine and firocoxib are currently under way. Another pharmacokinetic study was completed with butorphanol, a morphinan-type synthetic agonist-antagonist opioid also used for analgesia (Tana et al, 2010).…”

Phylogenetic analysis of the cytochrome P450 (CYP450) nucleotide sequences of the horse and predicted CYP450s of the white rhinoceros (Ceratotherium simum) and other mammalian species

“…While large numbers of different species, diseases and conditions require medical attention and treatment, wildlife veterinarians are often faced with the lack of approved and scientifically evaluated drugs for zoo and wildlife species. A study published by Tana et al (2010) stated that only 8–10 compounds are approved for the use in zoo and wildlife in the USA in contrast to close to 300 in cattle. The white rhino represents one of the species where basic medical knowledge is not yet readily available.…”

Results of the Megavertebrate Analgesia Survey: Elephants and Rhino

“…While online and published formularies exist, there is an extremely limited number of scientific studies performed on the pharmacokinetics of analgesics in elephants. 1,2,5,9,10,15,16 To date, there are no specific pharmacokinetic studies available in any species of rhinoceros to support dosing regimens for drugs used for pain management. Published studies 8,9,12,13 of opioids administered to rhinoceros having focused on administration for sedation and general anesthesia, not analgesia.…”

“…In addition, many published doses in both formularies and case reports for these species are not based on actual pharmacokinetic studies but instead are extrapolated from doses administered in domestic horses. 4,5,9,10,[12][13][14][15] To better characterize medications, usage patterns, and methods of providing analgesia to megavertebrates, a link to an online survey ( Data collected about drugs utilized and modality of analgesia provided were compiled using Microsoft Access into the following categories: facility information; signalment (age, genus, and species); drug or modality, including name and specific drug formulation utilized; and dosing regimen, including route, drug vehicle, dose in ''mg/kg,'' dosing interval, and duration. Patient information regarding pain treated was also collected.…”

“…Sedation associated with opioid drug administration to both elephants and rhinoceroses is an expected side effect, especially considering the known sensitivities to these drugs and their use as anesthesia drugs in these species. [7][8][9][10]12,13,15,16 Improved information from pharmacokinetic trials of these drugs will likely alleviate these negative dose-related effects.…”