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Journal of veterinary pharmacology and therapeutics2021; 45(2); 196-202; doi: 10.1111/jvp.13036

Phenylbutazone pharmacokinetics in southern white rhinoceros (Ceratotherium simum simum) after oral administration.

Abstract: Southern white rhinoceros (Ceratotherium simum simum) frequently develop painful conditions, such as traumatic injuries or osteoarthritis, necessitating the administration of pain-relieving medications. One of the preferred treatments is the nonsteroidal anti-inflammatory drug phenylbutazone because of the availability of oral formulations and the familiarity of its use in horses. For the main study, a single oral dose of phenylbutazone at 2 mg/kg was administered to healthy adult rhinoceros (n = 33) housed at six North American zoological institutions. Each rhinoceros had up to four blood samples collected under voluntary behavioural restraint at up to four predetermined time points (0, 1, 1.5, 2, 3, 4, 6, 8, 10, 24, 30 and 48 h). Drug analysis was performed by high-performance liquid chromatography. The population pharmacokinetic parameters were calculated with nonlinear mixed-effects modelling, and analysis showed a peak concentration (CMAX ) of 3.8 µg/ml at 1.8 h and an elimination half-life of 9 h. The concentrations achieved were similar to what has been reported for horses and were within the half maximal effective concentration for horses for at least 10 h. A multi-dose trial in five rhinoceros receiving 2 mg/kg orally once daily for five days found mild accumulation at a predicted factor of 1.2. This study represents the first pharmacokinetic data of phenylbutazone in any rhinoceros species.
© 2021 John Wiley & Sons Ltd.
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Publication Date: 2021-12-11 PubMed ID: 34894412DOI: 10.1111/jvp.13036Google Scholar: Lookup
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Summary

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This research article assesses the effectiveness and behavior of the anti-inflammatory drug phenylbutazone in southern white rhinoceros. Administered orally, the drug exhibited a peak concentration at 1.8 hours and an elimination half-life of 9 hours, similar to responses recorded in horses. Accumulation of the drug was determined to be mild in a multiple-dose trial.

Research Context

  • The southern white rhinoceros often experiences painful conditions like traumatic injuries or osteoarthritis, requiring pain management drugs.
  • A commonly used medication is the non-steroidal anti-inflammatory drug, phenylbutazone, due to its easy oral application and familiarity from its use in horses.

Research Methodology

  • The research involved administering a single dose of 2 mg/kg of phenylbutazone to 33 healthy adult rhinoceros across six North American zoos.
  • The researchers took four blood samples from each animal at specified intervals ranging from immediately after administration up to 48 hours later.
  • An analysis of the drug was carried out using high-performance liquid chromatography.

Research Results

  • With the use of nonlinear mixed-effects modeling, they determined the population pharmacokinetic parameters.
  • The calculated peak concentration (C) was 3.8 µg/ml, occuring 1.8 hours after administration with an elimination half-life of 9 hours.
  • The results matched those reported for horses and remained within the half maximal effective concentration for horses for nearly 10 hours.

Additional Study

  • The researchers also conducted a multi-dose trial in which five rhinoceros received 2 mg/kg orally once daily for five consecutive days.
  • Results showed a mild accumulation of the drug at a predicted factor of 1.2.
  • This research provides the inaugural set of pharmacokinetic data for any rhinoceros species subjected to phenylbutazone treatment.

Cite This Article

APA
Houck EL, Papich MG, Delk KW. (2021). Phenylbutazone pharmacokinetics in southern white rhinoceros (Ceratotherium simum simum) after oral administration. J Vet Pharmacol Ther, 45(2), 196-202. https://doi.org/10.1111/jvp.13036

Publication

Journal of veterinary pharmacology and therapeutics
ISSN: 1365-2885
NlmUniqueID: 7910920
Country: England
Language: English
Volume: 45
Issue: 2
Pages: 196-202

Researcher Affiliations

Houck, Emma L
  • North Carolina State University College of Veterinary Medicine, Raleigh, North Carolina, USA.
Papich, Mark G
  • North Carolina State University College of Veterinary Medicine, Raleigh, North Carolina, USA.
Delk, Katie W
  • North Carolina Zoo, Asheboro, North Carolina, USA.

MeSH Terms

  • Administration, Oral
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal
  • Horses
  • Perissodactyla
  • Phenylbutazone

Grant Funding

  • International Rhino Foundation
  • American Association of Zoo Veterinarians

References

This article includes 33 references
  1. AZA Population Management Center (2020). Survival statistics library. https://www.aza.org/species-survival-statistics
  2. Baggot JD. Bioavailability and bioequivalence of veterinary drug dosage forms, with particular reference to horses: an overview. Journal of Veterinary Pharmacology and Therapeutics 15(2), 160-173.
    doi: 10.1111/j.1365-2885.1992.tb01003.xgoogle scholar: lookup
  3. Bechert U, Christensen JM, Ngyuyen C, Neelkant DR, Bendas E. Pharmacokinetics of orally administered phenylbutazone in African and Asian elephants (Loxodonta africana and Elephas maximus). Journal of Zoo and Wildlife Medicine 39(2), 188-200.
    doi: 10.1638/2007-0139r.1google scholar: lookup
  4. Bon C, Toutain PL, Concordet D, Gehring R, Martin-Jimenez T, Smith J, Pelligand L, Martinez M, Whittem T, Riviere JE, Mochel JP. Mathematical modeling and simulation in animal health. Part III: Using nonlinear mixed-effects to characterize and quantify variability in drug pharmacokinetics. Journal of Veterinary Pharmacology and Therapeutics 41(2), 171-183.
  5. Charles B. Population pharmacokinetics: an overview. Australian Prescriber 37(6), 210-213.
    doi: 10.18773/austprescr.2014.078google scholar: lookup
  6. Cromsigt JPGM, te Beest M. Restoration of a megaherbivore: landscape-level impacts of white rhinoceros in Kruger National Park, South Africa. Journal of Ecology 102(3), 566-575.
    doi: 10.1111/1365-2745.12218google scholar: lookup
  7. East B, Tell L, Citino SB, Fredholm DV, Gamble K. Pharmacokinetics of a single oral dose of flunixin meglumine in the white rhinoceros (Ceratotherium simum). Journal of Zoo and Wildlife Medicine 50(2), 322.
    doi: 10.1638/2018-0200google scholar: lookup
  8. Emslie RH, Milliken T, Talukdar B, Burgess G, Adcock K, Balfour D, Knight MH. African and Asian Rhinoceroses-Status, Conservation and Trade A report from the IUCN Species Survival Commission (IUCN SSC) African and Asian Rhino Specialist Groups and TRAFFIC to the CITES Secretariat pursuant to Resolution Conf. 9.14 (Rev. CoP17). .
  9. Esson DW, Wellehan JFX, Lafortune M, Valverde A, Citino SB. Surgical management of a malacic corneal ulcer in a greater one-horned Asian rhinoceros (Rhinoceros unicornis) using a free island tarsoconjunctival graft. Veterinary Ophthalmology 9(1), 65-69.
    doi: 10.1111/j.1463-5224.2005.00440.xgoogle scholar: lookup
  10. Ette EI, Williams PJ, Lane JR. Population pharmacokinetics III: Design, analysis, and application of population pharmacokinetic studies. Annals of Pharmacotherapy 38(12), 2136-2144.
    doi: 10.1345/aph.1e260google scholar: lookup
  11. Galateanu G, Hildebrandt TB, Maillot A, Etienne P, Potier R, Mulot B, Saragusty J, Hermes R. One small step for rhinos, one giant leap for wildlife management-imaging diagnosis of bone pathology in distal limb. PLoS One 8(7), 68493.
    doi: 10.1371/journal.pone.0068493google scholar: lookup
  12. Greunz EM, Simon M, Lemberger K, Galateanu G, Hermes R, Leclerc A. Clinical management of bilateral cutaneous squamous cell carcinoma of the hind feet pads in a southern white rhinoceros (Ceratotherium simum simum). Journal of Zoo and Wildlife Medicine 47(2), 645-649.
    doi: 10.1638/2016-0001.1google scholar: lookup
  13. Hamerton B-CAE. Review of mortality rates and report on the deaths occurring in the society’s gardens during the year 1938. Proceedings of the Zoological Society of London 3-4, 281-289.
    doi: 10.1111/j.1096-3642.1939.tb00717.xgoogle scholar: lookup
  14. Harrison TM, Stanley BJ, Sikarskie JG, Bohart G, Ames NK, Tomlian J, Marquardt M, Marcum A, Kiupel M, Sledge D, Agnew D. Surgical amputation of a digit and vacuum-assisted-closure (V.A.C.) management in a case of osteomyelitis and wound care in an eastern black rhinoceros (Diceros bicornis michaeli). Journal of Zoo and Wildlife Medicine 42(2), 317-321.
    doi: 10.1638/2010-0149.1google scholar: lookup
  15. Higgins AJ, Lees And P, Taylor JB. Influence of phenylbutazone on eicosanoid levels in equine acute inflammatory exudate. The Cornell Veterinarian 74(3), 198-207.
  16. Kottwitz J, Boothe M, Harmon R, Citino SB, Zuba JR, Boothe DM. Results of the megavertebrate analgesia survey: Elephants and rhino. Journal of Zoo and Wildlife Medicine Wildlife Medicine 47(1), 301-310.
    doi: 10.1638/2015-0195.1google scholar: lookup
  17. Lees P, Landoni MF, Giraudel J, Toutain PL. Pharmacodynamics and pharmacokinetics of nonsteroidal anti-inflammatory drugs in species of veterinary interest. Journal of Veterinary Pharmacology and Therapeutics 27(6), 479-490.
    doi: 10.1111/j.1365-2885.2004.00617.xgoogle scholar: lookup
  18. Leiberich M, Krebber R, Hewetson M, Marais J, Naidoo V. A study of the pharmacokinetics and thromboxane inhibitory activity of a single intramuscular dose of carprofen as a means to establish its potential use as an analgesic drug in white rhinoceros. Journal of Veterinary Pharmacology and Therapeutics 41(4), 605-613.
    doi: 10.1111/jvp.12508google scholar: lookup
  19. Leiberich M, Marais HJ, Naidoo V. 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. PeerJ 2018(10), e5718.
    doi: 10.7717/peerj.5718google scholar: lookup
  20. Loeser RF. The Role of Aging in the Development of Osteoarthritis. Transactions of the American Clinical and Climatological Association 128, 44-54.
  21. Martin-Jimenez T, Riviere JE. Population pharmacokinetics in veterinary medicine: potential use for therapeutic drug monitoring and prediction of tissue residues. Journal of Veterinary Pharmacology And Therapeutics 21(3), 167-189.
  22. Meyer L, Bengis R, Fowlds W, Goddard A, Hofmeyr M, Marais J, Odell J, Steenkamp G, Tordiffe A, Kock M. Treatment of rhinoceros which have been poached using opioids and are found recumbent. South African Veterinary Association .
  23. Nance MB. Clinical management of severe necrotic laminar disease in an eastern black rhinoceros (Diceros bicornis michaeli) associated with an undetermined etiology. Proceedings of AAZV and AAWV Joint Conference 208-212.
  24. Papich MG. Phenylbutazone. Saunders Handbook of Veterinary Drugs pp. 629-631.
    doi: 10.1016/b978-0-323-24485-5.00452-6google scholar: lookup
  25. Regnault S, Hermes R, Hildebrandt T, Hutchinson J, Weller R. Osteopathology in the feet of rhinoceroses: lesion type and distribution. Journal of Zoo and Wildlife Medicine 44(4), 918-927.
    doi: 10.1638/2012-0277r1.1google scholar: lookup
  26. Rothschild BM, Prothero DR, Rothschild C. Origins of spondyloarthropathy in Perissodactyla. Clinical and Experimental Rheumatology 19, 628-632.
  27. Singh R, Srivastava U, Nasir M. Brief description of wound management in one horned rhinoceros in captivity. Indian Zoo Year Book 8, 123-126.
  28. Smit Y, Steyl J, Marais J. Solitary ostiochondroma of the distal third metacarpal bone in a two-year-old white rhinoceros (Ceratotherium simum). Journal of Zoo and Wildlife Medicine 47(4), 1086-1089.
    doi: 10.1638/2015-0261.1google scholar: lookup
  29. Species360 Zoological Information Management System. (2020b). ZIMS Global Drug Usage Extracts for Phenylbutazone in Ceratotherium simum (Accessed 28 Feb 2020). http://zims.species360.org
  30. Species360 Zoological Information Management System. (2020a). Population overview report for ceratotherium. http://zims.species360.org
  31. Stilson KT, Hopkins SSB, Davis EB. Osteopathology in rhinocerotidae from 50 million years to the present. PLoS One 11(2), e0146221.
    doi: 10.1371/journal.pone.0146221google scholar: lookup
  32. Toutain PL, Autefage A, Legrand C, Alvinerie M. Plasma concentrations and therapeutic efficacy of phenylbutazone and flunixin meglumine in the horse: pharmacokinetic/pharmacodynamic modelling. Journal of Veterinary Pharmacology and Therapeutics 17(6), 459-469.
    doi: 10.1111/j.1365-2885.1994.tb00278.xgoogle scholar: lookup
  33. Wack AN, Miller CL, Wood CE, Garner MM, Haefele HJ. Melanocytic neoplasms in a black rhinoceros (Diceros bicornis) and an Indian rhinoceros (Rhinoceros unicornis). Journal of Zoo and Wildlife Medicine 41(1), 95-103.
    doi: 10.1638/2009-0085.1google scholar: lookup

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