Bioavailability of Oral Ondansetron in Dogs: A Crossover Study

The purpose of this study was to evaluate the pharmacokinetics of oral (PO) ondansetron compared to intravenous (IV) ondansetron in eight healthy client-owned dogs. Dogs were randomized to one of two protocols in a crossover design, receiving PO or IV ondansetron at a dose of 1 mg/kg on Day 0 and the opposite formulation at an equal dose on Day 7. Plasma was collected at baseline and 1, 2, 4, and 8 h post administration. Ondansetron concentrations were measured utilizing liquid chromatography/mass spectrometry. For IV administration, AUC_0-8h was 1181 ± 619 ng/mL*h, with all dogs having detectable plasma concentrations at all time points. For PO administration, mean C_max was 22 ± 11.3 ng/mL and AUC_0-8h was 61.7 ± 45.4 ng/mL*h, with all dogs having undetectable concentrations at various time points. Oral mean bioavailability was estimated at 5.2% ± 2.1%. Oral bioavailability of ondansetron is very low in healthy dogs, raising concern for the efficacy of ondansetron when given orally at 1 mg/kg. Future studies evaluating pharmacodynamics of ondansetron in nauseous client-owned dogs should be performed to investigate whether plasma drug concentrations are the optimal way to assess the efficacy of oral ondansetron.