Abstract
The bioavailability of cinnarizine (CN) from three capsules was investigated in gastric-acidity-controlled rabbits (GAC-rabbits) with low and high acidities. Two commercial capsules (capsules A, B), which show poor dissolution in a low acidity medium, and one test capsule, whose dissolution in a low acidity medium was improved, were used. Rabbits with low acidity showed significantly lower Cmax and area under the plasma concentration-time curve (AUC) than rabbits with high acidity after administration of capsules A and B. Capsule A showed higher Cmax and AUC than capsule B in rabbits with low acidity. The difference of bioavailability between the two capsules appears to be due to difference of dissolution rate, depending on the gastric pH. The results obtained in this study corresponded very well with the results obtained in humans. Consequently, we conclude that the GAC-rabbit is a promising animal model for testing the bioavailability of a drug preparation showing gastric acidity-dependent bioavailability in humans. On the other hand, the bioavailability of CN from the test capsule was not affected by gastric acidity. Therefore, a small inter-subject variation of CN bioavailability can be expected on oral administration of the test capsule.
