Size discrimination in rat and mouse gastric emptying.
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OBJECTIVES: To investigate the relationship between particle size and gastric emptying in rodents using radiolabeled insoluble polymethyl methacrylate (PMMA) microcapsules/beads. METHODS: PMMA microcapsules (50-500m) and beads (0.5-3mm) loaded with technetium-99m diethylenetriamine pentaacetic acid ((99m) Tc-DTPA) were administered to ICR mice or Sprague Dawley (SD) rats by oral gavage. Gamma scintiscans were acquired initially following administration and then at hourly intervals to 4hours. RESULTS: Scintiscans revealed that the smallest PMMA microcapsules (50-100m) or beads (0.5-1mm) were impeded in the stomach and emptied slower than large particles in both rodent species. In mice, no significant difference in gastric emptying was found with microcapsules between 100 and 300m in diameter (p=0.25) and particles more than 300m could not be administered. In rats, capsules containing 0.5-3mm beads were stuck to the esophagus (up to 1hour), this was a limitation of dosing beads of this size because they cannot be suspended in a liquid media for oral gavage purposes. Beads with diameters of 2-3mm stayed in the stomach for up to 4hours. CONCLUSIONS: The cut-off emptying size in ICR mice could not be determined, due to the limitation of current available dosing methods. The cut-off emptying size in SD rats was between 1.5 and 2mm. Therefore, particles with a diameter greater than 2mm should not be used for gastric emptying studies of intact particles in SD rats, as their emptying is retarded in the stomach.