Prokinetic effects of large-dose lubiprostone on gastrointestinal transit in dogs and its mechanisms

Objective: To systemically explore effects of large dose of lubiprostone on gastrointestinal (GI) transit and contractions and its safety in dogs. Methods: 12 healthy dogs were studied. 6 dogs were operated to receive duodenal cannula and colon cannula and the other 6 dogs received gastric cannula. Lubiprostone was orally administrated at a dose of 24 μg or 48 μg 1 hr prior to the experiments. Gastric emptying (GE) of solids and small bowel transit were evaluated by collecting the effluents from the duodenal cannula and from the colon cannula. Gastric accommodation was measured by barostat. Gastric and intestinal contractions were by manometry. Colon transit was by X-ray pictures. Results: 1) Lubiprostone 48 μg not 24 μg accelerated GE. Atropine could block the effect; 2) Average motility index (MI) of gastric antrum in lubiprostone 48 μg session was significantly higher in both fasting state (P = 0.01) and fed state (P = 0.03). Gastric accommodation was not significantly different; 3) Lubiprostone 48 μg accelerated small bowel and colon transit. Atropine could block the effect on small bowel transit; 4) Lubiprostone 48 μg increased postprandial small bowel MI (P = 0.0008) and colon MI (P = 0.002). 5) No other adverse effects except for diarrhea were observed. Conclusion: Acute administration of lubiprostone at a dose of 48 μg accelerates GI motility and enhances GI contractions in the postprandial state. The findings suggest that lubiprostone may have an indirect prokinetic effects on the GI tract and vagal activity may be involved. Lubiprostone may be safely used.