Species variation in gastric toxicity following chronic administration of ciprofibrate to rat, mouse, and marmoset.

Comparative oral toxicity studies with ciprofibrate have been undertaken in the mouse, rat, and marmoset for up to 26 weeks. Chronic administration of ciprofibrate (20 mg/kg/day) produced a prolonged, modest, but statistically significant hypergastrinemia in the rat. Morphological changes in the rat stomach included increased eosinophilia and hypertrophy of oxyntic cells after 2 or more weeks treatment and hyperplasia of the neuroendocrine (NE) cells after 8 weeks treatment. In contrast, only a transient hypergastrinemia was induced, but not sustained in the mouse at the same dose level over an 8-week time period. No morphological changes were detected in the stomach of this species. In the marmoset treatment, up to 80 mg/kg/day for 26 weeks failed to induce hypergastrinemia and no significant alterations in gastric NE cells were detected.