Animal Models For Gastric Emptying

Dogs are widely used to assess the absorption of drugs. However, the drug absorption profiles differ quite considerably from those in humans, and this is a particular problem when attempting to obtain useful data for either sparingly water-soluble drugs or sustained release preparations.

The anatomy and dimensions of the upper gastrointestinal tract of dogs and humans are essentially similar. The volume of the stomach is 1-1.6 L in man and about 1 L in dogs. The length of the duodenum is 25 cm in both species and the jejunum is 185-250 cm in dogs and 300 cm in man. The diameter of the small intestine is 2-2.5 cm in dogs and 3-4 cm in man. The ileum and colon are substantially shorter in dogs than man.

During fasting, intragastric pH in man varies between 1.3-1.8, but the corresponding pH in the dog is between 0.8 and 8. Kuna103 reported that 77% of 403 dogs had a fasting pH of 6 or above. Sometimes the resting gastric pH is indistinguishable from the duodenal pH. The rate of acid secretion is much lower in dogs, being 0.1 mEqh-1 compared to 2-5 mEqh- 1 in man.

It is also thought that dogs have a faster total gastrointestinal transit time than man, and hence bioavailability is generally underestimated. However, in dogs, a normal meal can induce a fed pattern for approximately 12 to 14 hours, but in humans this usually only lasts for between 3 to 4 hours. Rigidity is an important factor in the retention of dosage forms. In dogs, rigid rings with a diameter of 3.6 cm are well retained in the stomach for 24 hours, whilst pellets and strings demonstrated rapid emptying105. In dogs pellets tend to empty from the stomach entrapped in plugs of mucus106. Dogs have a delayed onset of MMC compared to man107 108.

Pigs are also not a good model for the gastrointestinal transit of large non-disintegrating capsules. One study demonstrated a gastric residence time of 5 days for an enteric coated non-disintegrating magnesium hydroxide caplet (1.5 g ml density, 19.6x9.5 mm, 1.2 g weight)109. As a result of these differences, studies of oral dose forms in animals must be interpreted with caution, particularly if the operation of the formulation depends on its detailed behaviour in the gastrointestinal tract.

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