Delayed gastric emptying is suspected to occur in several common conditions in dogs, for example metabolic/endocrine disorders or inflammatory bowel disease. It can also be a sequela in critical care patients suffering from sepsis, peritonitis or pancreatitis. Treating the underlying cause is indicated, but additional supportive treatment in the form of prokinetic drugs is scarce, especially as 5-HT4 receptor agonists are not widely available. The antidepressant mirtazapine, routinely used at low dosages for its appetite stimulating properties in small animals, has been reported to accelerate gastric emptying both in people and (at high dosages) in experimental healthy dogs. The effects of mirtazapine on gastric emptying times using a non-invasive test have not been assessed. Hence, assessing the effect of different dosages of this drug on gastric half emptying times (G50%) in healthy dogs using the ¹³C-SABT was sought.

Six healthy Beagle dogs (3–5 years, 9.7–11.6 kg body weight) were included. Mirtazapine was used at increasing dosages (0.6 mg/kg=MLo, 2 mg/kg=MMe, 20 mg/kg=MHi). Initially, MLo, placebo and prucalopride (1 mg/kg as a positive control) were administered orally in a cross-over design. Subsequently, MMe and MHi were administered and compared to a second and third placebo treatment. This approach was chosen to enable interim analysis of data, as ethical approval only allowed to progress to a higher mirtazapine dose if no effect was seen with the lower one. On day 4 of each treatment, a test meal consisting of each dog's half daily calorie requirement and 150 mg ¹³C-sodium acetate was fed after an overnight fast and a ¹³C-SABT was performed. Breath samples were obtained with a facial mask before (0 minutes) and 30, 60, 120, 180, 240, 300, and 360 minutes after test meal ingestion. ¹²CO₂/¹³CO₂ ratio in the breath was measured by non-dispersive infrared spectroscopy and delta-over baseline (DOB) values plotted against time. G50% was calculated for each treatment based on cumulative non-linear curve fitting of the DOB values. Median G50% was 78.3 minutes (range 48.4–93.3) with MLo, 84.4 minutes (69.2–109.6) with MMed and 106.4 minutes (range 83.1–144.2) with MHi. Median G50% for prucalopride and for placebo was 61.9 minutes (43.1–159.0) and 67.1 minutes (38.1–146.1), respectively.

MLo (p=0.75) and MMed (p=0.12) had no effect on G50% compared to placebo. Unexpectedly, MHi prolonged gastric emptying (p=0.046). G50% was not significantly different between prucalopride and placebo (p=0.75). In conclusion, mirtazapine does not accelerate G50% in healthy dogs. In high dosages, it might prolong gastric emptying, even though with borderline significance.

Disclosures

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