Approbation of the cisplatin-induced acute vomiting model in ferret and choice of reference treatment

A.E. Katelnikova, PhD, Toxicology Team Leader,
A.A. Zueva, Toxicologist,
A.A. Matichin, Pharmacologist,
D.R. Kargopolceva, Veterinarian,
D.S. Gajdaj, Biologist

Institute of Preclinical Research Ltd.
188663, Russia, Leningrad oblast, Vsevolozhskiy district, Kuzmolovskiy t.s., Zavodskaya st. 3-245



The absent of effective in all clinical and other conditions nausea and vomiting antiemetic treatment demonstrate the need for research in this area. This raises the question, what models are most suitable for such studies. In the early 1980’s it was seen ferrets suffered from acute vomiting induced by high dose of cisplatin. It was suggested using ferrets as an alternative test-system instead dogs, cats and monkeys which exploited previously in researches of vomiting induced by cytotoxics and testing of potential antiemetic medicines. Cisplatin-induced vomiting in ferret has used more than 30 years. It allowed stablishing and implementing antiemetic medicines such as ondansetron, granisetron, aprepit, fosaprepitant in clinical usage. The aim of this study was approbation of cisplatin-induced acute vomiting in ferret with formulation of choice reference medicines. Ferrets were separated into 3 groups of 4 animals. Three groups were administrated intraperitoneally cisplatin in 10 mg/kg. Ondasetron was administrated intramuscularly to animals in dose 1 mg/kg. Emend V/V was administrated intravenous to animals in dose 3 mg/kg. Follow indicators were chosen: latent period, number of retching or vomiting, which was registered on typical signs during 4 hours since the cisplatin administration. Our study demonstrates that the average latent period was 2 hours and summary number of retching or vomiting was 41 ± 17 (M±SD) in control group. Ondasetron and Emend V/V showed pronounced antiemetic effect expressed by significantly decrease retching and it wasn’t registered developing vomiting in ferrets. The administration of referent medicines didn’t effect on duration latent period. When data were interpreted there were taken into account factors affecting the reproducing of the model like administration route of pathological inductor, using of anesthesia, animal number in each group and the source where the animals were grown as the most non-obvious factor.

Full text available in Russain only.


  1. Andrews P.L.R., Horn C.C. Signals for nausea and emesis: Implications for models of upper gastrointestinal diseases. Auton. Neurosci. 2006. Vol. 125 (1–2): 100–15. DOI:10.1016/j.autneu.2006.01.008.
  2. Владимирова Л.Ю., Гладков О.А., Когония Л.М., Королева И.А., Семиглазова Т.Ю. Практические рекомендации по профилактике и лечению тошноты и рвоты у онкологических больных. Злокачественные опухоли. 2017; 7 (3-S2): 466–76. [Vladimirova L.YU., Gladkov O.A., Kogoniya L.M., Koroleva I.A., Semiglazova T.YU. Prakticheskie rekomendacii po profilaktike i lecheniyu toshnoty i rvoty u onkologicheskih bol'nyh. Zlokachestvennye opuholi. 2017; 7 (3-S2): 466–76 (in Russ)].
  3. Holmes A.M., Rudd J.A., Tattersall F.D., Aziz Q., Andrews P.L.R. Opportunities for the replacement of animals in the study of nausea and vomiting. Br. J. Pharmacol. 2009. Vol. 157 (6): 865–80. DOI: 10.1111/j.1476-5381.2009.00176.x.
  4. Davis C.J. Emesis research: a concise history of the critical concepts and experiments. J. R. Nav. Med. Serv. 1997. Vol. 83 (1): 31–41.
  5. Florczyk A.P., Schurig J.E., Bradner W.T. Cisplatin-induced emesis in the Ferret: a new animal model. Cancer. Treat. Rep. 1982. Vol. 66 (1): 187–9.
  6. Christie D.A., Tansey E.M. The discovery, use and impact of platinum salts as chemotherapy agents for cancer: The transcript of a Witness Seminar held by the Wellcome Trust Centre for the History of Medicine at UCL, London, on 4 April 2006. Wellcome Trust: London. 2007: 148.
  7. Hesketh P.J. Chemotherapy-induced nausea and vomiting. N. Engl. J. Med. 2008. Vol. 358 (23): 2482–494. DOI: 10.1056/NEJMra0706547.
  8. Ho K.Y., Gan T.J. Pharmacology, pharmacogenetics, and clinical efficacy of 5-hydroxytryptamine type 3 receptor antagonists for postoperative nausea and vomiting. Curr. Opin. Anesthesiol. 2006. Vol. 19 (6): 606–11. DOI: 10.1097/
  9. Pickering M., Jones J.F.X. The diaphragm: two physiological muscles IN one. J. Anat. 2002. Vol. 201 (4): 305–12. DOI: 10.1046/j.1469-7580.2002.00095.x.
  10. Alam J., Subhan F., Ullah I., Shahid M., Ali G., Sewell R.D. Synthetic and natural antioxidants attenuate cisplatin-induced vomiting. BMC Pharmacol. Toxicol. 2017. Vol. 18 (1): 4. DOI: 10.1186/s40360-016-0110-9.
  11. Du Sert N.P., Rudd J.A., Apfel C.C., Andrews P.L.R. Cisplatin-induced emesis: systematic review and meta-analysis of the ferret model and the effects of 5-HT 3 receptor antagonists. Cancer Chemother. Pharmacol. 2011. Vol. 67(3): 667–86. DOI: 10.1007/s00280-010-1339-4.
  12. Bolognini D., Rock E.M., Cluny N.L., Cascio M.G., Limebeer C.L., Duncan M., Pertwee R.G. Cannabidiolic acid prevents vomiting in S uncus murinus and nausea-induced behaviour in rats by enhancing 5-HT1A receptor activation. Br. J. Pharmacol. 2013. Vol. 168 (6): 1456–70. DOI: 10.1111/bph.12043.
  13. Horn C.C., Meyers K., Pak D., Nagy A., Apfel C.C., Williams B.A. Post-anesthesia vomiting: Impact of isoflurane and morphine on ferrets and musk shrews. Physiol. Behav. 2012. Vol. 106 (4): 562–8. DOI: 10.1016/j.physbeh.2012.03.031.
  14. Horn C.C., Henry S., Meyers K., Magnusson M.S. Behavioral patterns associated with chemotherapy-induced emesis: a potential signature for nausea in musk shrews. Front. Neurosci. 2011. Vol. 5: 88. DOI: 10.3389/fnins.2011.00088.
  15. Инструкция по медицинскому применению препарата Ондансетрон®. 2019. [Instrukciya po medicinskomu primeneniyu preparata Ondansetron®. 2019]. Available at: (accessed 18.08.2019).
  16. Tsuchiya M., Fujiwara Y., Kanai Y., Mizutani M., Shimada K., Suga O., Nagahisa, A. Anti-emetic activity of the novel nonpeptide tachykinin NK1 receptor antagonist ezlopitant (CJ-11,974) against acute and delayed cisplatin-induced emesis in the ferret. Pharmacol. 2002. Vol. 66 (3): 144–52.
  17. Tattersall F.D., Rycroft W., Francis B., Pearce D., Merchant K., MacLeod A.M., Cascieri M. Tachykinin NK1 receptor antagonists act centrally to inhibit emesis induced by the chemotherapeutic agent cisplatin in ferrets. Neuropharmacol. 1996. Vol. 35 (8): 1121–9. DOI:10.1016/s0028-3908(96)00020-2.
  18. Gardner C.J., Bountra C., Bunce K.T., Dale T.J., Jordan C.C., Twissell D.J., Ward P. Anti-emetic activity of neurokinin NK1 receptor antagonists is mediated centrally in the ferret. Br. J. Pharmacol. 1994. Vol. 112: 516.
  19. Duffy R.A., Morgan C., Naylor R., Higgins G.A., Varty G.B., Lachowicz J.E., Parker E.M. Rolapitant (SCH 619734): a potent, selective and orally active neurokinin NK1 receptor antagonist with centrally-mediated antiemetic effects in ferrets. Pharmacol. Biochem. Behav. 2012. Vol. 102 (1): 95–100. DOI: 10.1016/j.pbb.2012.03.021.
  20. Watson J.W., Gonsalves S.F., Fossa A.A., McLean S., Seeger T., Obach S., Andrews P.L.R. The anti-emetic effects of CP-99,994 in the ferret and the dog: role of the NK1 receptor. Br. J. Pharmacol. 1995. Vol. 115 (1): 84–94. DOI: 10.1111/j.1476-5381.1995.tb16324.x.
  21. Gonsalves S.F., Watson J.W., Ashton C.A. Broadspectrum antiemetic effects of CP-122,721, a tachykinin NK1 receptor antagonist, in ferrets. Eur. J. Pharmacol. 1996. Vol. 305: 181–5. DOI: 10.1016/0014-2999(96)00216-6.
  22. Grelot L., Dapzol J., Esteve E., Frugiere A., Bianchi A.L., Sheldrick R.L., Gardner C.J., Ward P. Potent inhibition of both the acute and delayed emetic responses to cisplatin in piglets treated with GR205171, a novel highly selective tachykinin NK1 receptor antagonist. Br. J. Pharmacol. 1998. Vol. 124: 1643–50. DOI: 10.1038/sj.bjp.0702019.
  23. Инструкция по медицинскому применению препарата Эменд В/В®. 2017. [Instrukciya po medicinskomu primeneniyu preparata Emend V/V®. 2017]. Available at: (accessed 18.08.2019).
  24. Приказ Министерства здравоохранения Российской Федерации № 199н от 01.04.2016 "Об утверждении Правил надлежащей лабораторной практики". [Prikaz Ministerstva zdravoohraneniya Rossijskoj Federacii ot 01.04.2016 № 199n "Ob utverzhdenii Pravil nadlezhashchej laboratornoj praktiki" (in Russ)].
  25. Решение Совета ЕЭК № 81 от 03.11.16 «Об утверждении Правил надлежащей лабораторной практики Евразийского экономического союза в сфере обращения лекарственных средств». [Reshenie Soveta EEK № 81 ot 03.11.16 «Ob utverzhdenii Pravil nadlezhashchej laboratornoj praktiki Evrazijskogo ekonomicheskogo soyuza v sfere obrashcheniya lekarstvennyh sredstv» (in Russ)].
  26. Minami M., Endo T., Kikuchi K., Ihira E., Hirafuji M., Hamaue N., Kisara K. Antiemetic effects of sendide, a peptide tachykinin NK1 receptor antagonist, in the ferret. Eur. J. Pharmacol. 1998. Vol. 363 (1): 49–55. DOI:10.1016/s0014-2999(98)00784-5.

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