Pharmacokinetics and Clinical Effects of a Single Oral Dose of Trazodone in Domestic Goats (Capra hircus) as a Model for Wild Ruminants
American Association of Zoo Veterinarians Conference 2019
Yasmeen Prud’homme1, DMV; Shannon T. Ferrell2, DVM, DABVP (Avian Practice), DACZM; Sylvain Nichols1, DMV, MSc, DACVS; Francis Beaudry1, PhD; Marion Desmarchelier1, DMV, MSc, DACZM, DECZM (Zoo Health Management), DACVB
1Faculté de Médecine Vétérinaire, Université de Montréal, Saint Hyacinthe, QC, Canada; 2Société Zoologique de Granby, Granby, QC, Canada

Abstract

Trazodone is an anti-anxiety medication commonly used in human and veterinary medicine.1,3 Stress-related trauma is the leading cause of morbidity and mortality in wild ruminant species. Trazodone could reduce stress and allow safer capture and handling, thus having a positive effect on their welfare. To the authors’ knowledge, trazodone use has never been documented in ruminants. The objective of this study was to describe the clinical effects and pharmacokinetic profile of an oral dose of trazodone (Teva-trazodone®, 50 mg tablets, Teva Canada Limited, Toronto, ON, Canada) in domestic goats (Capra hircus) as a model for wild ruminants. A pilot study using ethograms and actimetry (Actiwatch64, AW64-AM, CamNtech Ltd, Cambridge, UK) identified an oral dose of 10 mg/kg as optimal to reduce activity levels. This dose resulted in a significant increase in time spent sleeping (p=0.0016) and lying down (p=0.008), and decrease in time spent grooming (p=0.023), moving (p=0.005) and observing (p=0.0002). Activity levels were significantly decreased for 4 h following administration (p=0.049). There were no observed adverse effects. Time spent eating or ruminating was not affected by trazodone administration (p>0.05). The final project evaluated the pharmacokinetics of a single oral dose of 10 mg/kg of trazodone in 7 goats. All animals achieved plasma concentrations over 130 ng/ml, a level considered therapeutic in humans and dogs.1,2 Mean elimination half-life was 10.55±6.80 h. All goats achieved Cmax in 5–15 min and still had detectable plasma levels at 24 h. Trazodone appears promising to decrease stress in exotic bovid species. Further research is warranted to establish its efficacy in other ruminant species and clinical situations.

Acknowledgments

The authors thank Colombe Otis and Eric Troncy for their guidance with the accelerometers, Guy Beauchamp for statistical assistance, as well as Clément Maincent for technical assistance. This study was supported by the Zoo de Granby Wildlife Health Research Grant and the Faculté de médecine vétérinaire Zoetis fund. The HPLC-MS/MS analyses were performed on instruments funded by the National Sciences and Engineering Research Council of Canada (F. Beaudry Research Tools and Instruments Grants no. 439748-2013).

Literature Cited

1.  Jay AR, Krotscheck U, Parsley E, Benson L, Kravitz A, Mulligan A, Silva J, Mohammed H, Schwark WS. Pharmacokinetics, bioavailability, and hemodynamic effects of trazodone after intravenous and oral administration of a single dose to dogs. Am J Vet Res. 2013;74:1450–1456.

2.  Mercolini L, Colliva C, Amore M, Fanali S, Raggi MA. HPLC analysis of the antidepressant trazodone and its main metabolite m-cpp in human plasma. J Pharm Biomed Anal. 2008;47:882–887.

3.  Stevens BJ, Frantz EM, Orlando JM, Griffith E, Harden LB, Gruen ME, Sherman BL. Efficacy of a single dose of trazodone hydrochloride given to cats prior to veterinary visits to reduce signs of transport- and examination-related anxiety. J Am Vet Med Assoc. 2016;249:202–207.

 

Speaker Information
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Yasmeen Prud’homme, DMV
Faculté de Médecine Vétérinaire
Université de Montréal
Saint Hyacinthe, QC, Canada


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