Size discrimination in rat and mouse gastric emptying

Biopharm Drug Dispos. 2013 Mar;34(2):107-24. doi: 10.1002/bdd.1828. Epub 2013 Jan 24.

Abstract

Objectives: To investigate the relationship between particle size and gastric emptying in rodents using radiolabeled insoluble polymethyl methacrylate (PMMA) microcapsules/beads.

Methods: PMMA microcapsules (50-500 µm) and beads (0.5-3 mm) loaded with technetium-99 m 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 4 hours.

Results: Scintiscans revealed that the smallest PMMA microcapsules (50-100 µm) or beads (0.5-1 mm) 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 300 µm in diameter (p = 0.25) and particles more than 300 µm could not be administered. In rats, capsules containing 0.5-3 mm beads were stuck to the esophagus (up to 1 hour), 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 2-3 mm stayed in the stomach for up to 4 hours.

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 2 mm. Therefore, particles with a diameter greater than 2 mm should not be used for gastric emptying studies of intact particles in SD rats, as their emptying is retarded in the stomach.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Gastric Emptying*
  • Gastrointestinal Tract / diagnostic imaging
  • Gastrointestinal Tract / metabolism
  • Male
  • Mice
  • Mice, Inbred ICR
  • Particle Size
  • Polymethyl Methacrylate / administration & dosage
  • Polymethyl Methacrylate / chemistry*
  • Radionuclide Imaging
  • Radiopharmaceuticals / administration & dosage
  • Radiopharmaceuticals / pharmacokinetics*
  • Rats
  • Rats, Sprague-Dawley
  • Technetium Tc 99m Pentetate / administration & dosage
  • Technetium Tc 99m Pentetate / pharmacokinetics*

Substances

  • Radiopharmaceuticals
  • Polymethyl Methacrylate
  • Technetium Tc 99m Pentetate