A Novel Method for Controlling Gastric Acidity in Fasted Dogs to Evaluate the Bioavailability of Oral Formulations

Abstract

The objective of this study was to build a novel method to control gastric acidity under fasting condition for evaluating the bioavailability of an oral formulation in dogs. As a method for controlling gastric acidity, pretreatments by intramuscular pentagastrin administration, oral hydrochloric acid administration and oral water administration were examined. Pentagastrin and hydrochloric acid pretreatments insufficiently decreased the gastric pH, in some cases, with the remaining contents in the stomach, i.e. feces or highly viscous mucus, to possibly prevent lowering of the pH as a cause. On the other hand, pretreatment by administration of water could successfully achieve two objectives: elimination of gastric contents and acidity control by increasing gastrointestinal peristalsis and gastric acid secretion. A comparative bioavailability study of orally dosed cinnarizine, which is a weakly basic drug with a pH-dependent solubility, conducted by water pretreatment in dogs showed a significantly higher plasma concentration-time profile than that in not-acidified dogs pretreated by a proton pump inhibitor, omeprazole dosed intravenously. This result confirmed the validity of the pretreatment by oral water as a method to control the gastric acidity in dogs. A simple and safe method for controlling gastric acidity without placing an excessive load on the dog by only administering water, which utilizes the physiological functions of animals, is considered highly reproducible and useful as a model for evaluating the bioavailability of oral formulations.