Characteristics of the Human Upper Gastrointestinal Contents in the Fasted State Under Hypo- and A-chlorhydric Gastric Conditions Under Conditions of Typical Drug - Drug Interaction Studies

Abstract

Objective: Evaluate the impact of reduced gastric acid secretion after administration of two acid-reducing agents on the physicochemical characteristics of contents of upper gastrointestinal lumen of fasted adults.

Materials and methods: Eight healthy male adults, fasted from food for 12 h, participated in a three-phase crossover study. Phase 1: No drug treatment prior to aspirations. Phase 2: Oral administration of 40 mg pantoprazole at ~9 am the last 3 days prior to aspirations and at ~7 am on aspiration day. Phase 3: Oral administration of 20 mg famotidine at ~7 pm prior to aspirations and at ~7 am on aspiration day. Samples from the contents of upper gastrointestinal lumen were aspirated for 50 min, after administration of 240 ml table water at ~9 am.

Results: Reduction of gastric acid secretion was accompanied by reduced buffer capacity, chloride ion concentration, osmolality and surface tension in stomach and by increased pH (up to ~0.7 units) in upper small intestine during the first 50 min post-water administration. The mechanism of reduction of acid secretion seems to be important for the buffer capacity in stomach and for the surface tension in upper gastrointestinal lumen.

Conclusions: Apart from gastric pH, reduced acid secretion affects physicochemical characteristics of contents of upper gastrointestinal lumen which may be important for the performance of certain drugs/products in the fasted state.

Keywords: achlorhydria; duodenal composition; fasted state; gastric composition; hypochlorhydria; upper gastrointestinal lumen.