Suitability of the cynomolgus monkey as an animal model for drug absorption studies of oral dosage forms from the viewpoint of gastrointestinal physiology.

Abstract

To determine the usefulness of the monkey as an animal model, which can predict in vivo performance of humans, the major gastrointestinal physiological parameters of this animal were evaluated. The pH of gastric juice collected by a fiberscope from the stomach in fasted cynomolgus monkeys showed a high acidity level, which ranged from 1.2 to 4.3. The gastric emptying time of oral dosage forms (solution, granules and tablets) showed that the larger size dosage forms seemed to be emptied more slowly, and three dosage forms were prolonged by feeding. The gastrointestinal agitation intensity of monkeys was estimated using controlled-release tablets of acetoaminophen, which showed a slow erosion rate. The in vivo release amount-time profiles of the tablet in fasted monkeys corresponded to their in vitro profiles with paddle agitation conditions of between 10 rpm and 50 rpm of the paddle method; this result was smaller than in dogs (100 rpm) but equivalent to that in humans (10 rpm). Further, the small intestinal transit time (SITT), estimated using a double marker method, ranged from 2.2 to 4.2 h in the fasting state and from 2.2 to 3.2 h in the fed state; the SITT was not significantly delayed by feeding. Comparison with the published data about dogs and humans showed these gastrointestinal physiological parameters of monkeys to be more similar to those of humans. Consequently, it is assumed that the monkey is useful as an animal model for bioavailability studies of oral dosage forms.