Anti-nausea effects and pharmacokinetics of ondansetron, maropitant and metoclopramide in a low-dose cisplatin model of nausea and vomiting in the dog: a blinded crossover study

BMC Vet Res. 2017 Aug 16;13(1):244. doi: 10.1186/s12917-017-1156-7.


Background: Nausea is a subjective sensation which is difficult to measure in non-verbal species. The aims of this study were to determine the efficacy of three classes of antiemetic drugs in a novel low dose cisplatin model of nausea and vomiting and measure change in potential nausea biomarkers arginine vasopressin (AVP) and cortisol. A four period cross-over blinded study was conducted in eight healthy beagle dogs of both genders. Dogs were administered 18 mg/m2 cisplatin intravenously, followed 45 min later by a 15 min infusion of either placebo (saline) or antiemetic treatment with ondansetron (0.5 mg/kg; 5-HT3 antagonist), maropitant (1 mg/kg; NK1 antagonist) or metoclopramide (0.5 mg/kg; D2 antagonist). The number of vomits and nausea associated behaviours, scored on a visual analogue scale, were recorded every 15 min for 8 h following cisplatin administration. Plasma samples were collected to measure AVP, cortisol and antiemetic drug concentrations.

Results: The placebo treated group vomited an average number of 7 times (range 2-13). None of the dogs in either the ondansetron or maropitant treated groups vomited during the observation period. The onset of nausea-like behaviour in the placebo-treated group occurred at t3.5h and peaked at t4.75h with nausea behaviour score of 58.5 ± 4.6 mm. Ondansetron and maropitant reduced overall the area under the curve of nausea behaviour score by 90% and 25%, respectively. Metoclopramide had no effect on either vomiting or nausea. Cisplatin-induced nausea and vomiting caused concomitant increases in AVP and cortisol. In the placebo-treated group, AVP and cortisol increased from t2.5h, peaked at t5h (11.3 ± 2.9 pmol L-1 and 334.0 ± 46.7 nmol/L, respectively) and returned to baseline by t8h. AVP and cortisol increases were completely prevented by ondansetron and only partially by maropitant, while metoclopramide had no effect. The terminal half-lives (harmonic mean ± pseudo SD) for ondansetron, maropitant and metoclopramide were 1.21 ± 0.51, 5.62 ± 0.77 and 0.87 ± 0.17 h respectively.

Conclusions: 5-HT3 receptor antagonist ondansetron demonstrates the greatest anti-emetic and anti-nausea efficacy of the three drugs. AVP and cortisol appear to be selective biomarkers of nausea rather than emesis, providing a means of objectively measuring of nausea in the dog.

Keywords: Antiemetic; Arginine vasopressin; Biomarker; Cisplatin; Cortisol; Emesis; Maropitant; Metoclopramide; Nausea; Ondansetron.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Antiemetics / pharmacology
  • Antiemetics / therapeutic use*
  • Arginine Vasopressin / analysis
  • Cisplatin / adverse effects*
  • Cross-Over Studies
  • Dogs
  • Female
  • Hydrocortisone / analysis
  • Male
  • Metoclopramide / pharmacology
  • Metoclopramide / therapeutic use*
  • Nausea / chemically induced
  • Nausea / prevention & control
  • Nausea / veterinary*
  • Ondansetron / pharmacology
  • Ondansetron / therapeutic use*
  • Quinuclidines / pharmacology
  • Quinuclidines / therapeutic use*
  • Vomiting / chemically induced
  • Vomiting / prevention & control
  • Vomiting / veterinary*


  • Antiemetics
  • Quinuclidines
  • Arginine Vasopressin
  • Ondansetron
  • maropitant
  • Metoclopramide
  • Cisplatin
  • Hydrocortisone