Pharmacokinetics of Orally Administered Phenylbutazone in African and Asian Elephants (Loxodonta africana and Elephas maximus)

Bechert, Ursula; Christensen, J. Mark; Nguyen, Cindy B.; Neelkant, R.; Bendas, Ehab R.

doi:10.1638/2007-0139r.1

Cited by 24 publications

(23 citation statements)

References 28 publications

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“…Importantly, zoo elephant research has repeatedly identified differences between African and Asian elephants. Different drug‐dosage requirements (Bechert et al ., ), reproductive pathologies (Hildebrandt et al ., ; Brown et al ., ), digestive physiologies (Dierenfeld, ; van Sonsbeek et al ., ), pheromones (Rasmussen & Schulte, ) and susceptibility to EEHV (Bronson, E., et al ., ) are a few such examples. Nonetheless, African and Asian elephants have typically been viewed and managed collectively as ‘elephants’ in captive settings.…”

Section: Discussionmentioning

confidence: 99%

“…For example, Bechert et al . () found significant differences ( P < 0·0001) between African and Asian elephants in mean residence time, terminal half‐life and clearance rates for phenylbutazone, along with evidence of enterohepatic cycling in Asian, but not African, elephants.…”

Section: Pharmacologymentioning

confidence: 96%

“…Drugs to treat non‐specific disease manifestations have focused on non‐steroidal anti‐inflammatories (NSAIDs), and phenylbutazone and flunixin meglumine are most commonly prescribed (Kottwitz et al ., ). Pharmacokinetic studies conducted with NSAIDs in elephants (Table ) include ibuprofen (Bechert & Christensen, ), ketoprofen (Hunter et al ., ), phenylbutazone (Bechert et al ., ), 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 ., ).…”

Section: Pharmacologymentioning

confidence: 99%

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

Bechert

Brown

Dierenfeld

et al. 2019

International Zoo Yearbook

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African elephants Loxodonta africana and Asian elephants Elephas maximus are not thriving in many captive settings and are threatened throughout their native ranges. Many zoos support in situ conservation projects and provide opportunities to conduct ex situ research in controlled settings with comparably approachable animals. Zoo elephant projects may facilitate fieldwork with free‐ranging elephants (e.g. development of non‐invasive sampling and analytical tools), which may then also improve the husbandry of elephants in human care. Free‐ranging elephants also benefit from drug therapies and veterinary care when they are orphaned, kept as working elephants or brought in as rehabilitation cases – especially as human–elephant conflicts become more common as a result of ever‐expanding human populations. Much has been learned about the basic biology and husbandry needs of elephants but, often, the more we learn, the more questions arise. There are physiological differences between African and Asian elephants, and this should affect the management of these animals. This paper will provide brief overviews of the current state of knowledge regarding the pharmacology, nutrition, reproduction, sensory biology and diseases (primarily elephant endotheliotropic herpesvirus infections) relevant to elephants with recommendations for future research.

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Section: Discussionmentioning

confidence: 99%

Section: Pharmacologymentioning

confidence: 96%

Section: Pharmacologymentioning

confidence: 99%

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

Bechert

Brown

Dierenfeld

et al. 2019

International Zoo Yearbook

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“…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.…”

Section: Brief Communicationmentioning

confidence: 99%

Results of the Megavertebrate Analgesia Survey: Elephants and Rhino

Kottwitz¹,

Boothe²,

Harmon³

et al. 2016

Journal of Zoo and Wildlife Medicine

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An online survey utilizing Survey Monkey linked through the American Association of Zoo Veterinarians listserve examined current practices in megavertebrate analgesia. Data collected included drugs administered, dosing regimens, ease of administration, efficacy, and adverse events. Fifty-nine facilities (38 housing elephants, 33 housing rhinoceroses) responded. All facilities administered nonsteroidal anti-inflammatory drugs (NSAIDs), with phenylbutazone (0.25-10 mg/kg) and flunixin meglumine (0.2-4 mg/kg) being most common. Efficacy was reported as "good" to "excellent" for these medications. Opioids were administered to elephants (11 of 38) and rhinoceroses (7 of 33), with tramadol (0.5-3.0 mg/kg) and butorphanol (0.05-1.0 mg/kg) being most common. Tramadol efficacy scores were highly variable in both elephants and rhinoceroses. While drug choices were similar among institutions, substantial variability in dosing regimens and reported efficacy between and within facilities indicates the need for pharmacokinetic studies and standardized methods of analyzing response to treatment to establish dosing regimens and clinical trials to establish efficacy and safety.

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“…29 Pain management is a beneficial addition to the treatment of lameness and can help decrease its severity. Currently, arthritic elephants are typically treated with a wide variety of nonsteroidal anti-inflammatory drugs and opioid analgesics, which offer only palliative treatment and have limited pharmacokinetic basis for dose determination, 2,3,19 despite the fact that these drugs can have serious side effects when used at inappropriate dosages. Due to the adverse effects of these agents in domestic species, accurate therapeutic regimens are critical to properly treating diseased elephants.…”

Section: Introductionmentioning

confidence: 99%

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

Tana

Isaza²,

Koch³

et al. 2010

Journal of Zoo and Wildlife Medicine

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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.

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Pharmacokinetics of Orally Administered Phenylbutazone in African and Asian Elephants (Loxodonta africana and Elephas maximus)

Cited by 24 publications

References 28 publications

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

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

Results of the Megavertebrate Analgesia Survey: Elephants and Rhino

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

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