Characterization of Contents of Distal Ileum and Cecum to Which Drugs/Drug Products are Exposed During Bioavailability/Bioequivalence Studies in Healthy Adults.

ABSTRACT

PURPOSE: Characterize the contents of distal ileum and cecum in healthy adults under conditions simulating the bioavailability/bioequivelance studies of drug products in fasted and fed state. METHODS: Twelve males participated in a two-phase crossover study. Phase I subjects remained fasted overnight plus 4.5 h in the morning prior to colonoscopy. Phase II subjects remained fasted overnight, consumed breakfast in the morning, and abstain from food until colonoscopy, 4.5 h after breakfast. Upon sampling, volume, pH and buffer capacity were measured; after ultracentrifugation, supernatant was physicochemically characterized and non-liquid particles diameter was measured. RESULTS: In distal ileum, pH is ~8.1 and size of non-liquid particles is ~200 µm, regardless of dosing conditions; in fed state, liquid fraction was lower whereas osmolality and carbohydrate content were higher. In cecum, the environment was similar with previously characterized environment in the ascending colon; in fasted state, size of non-liquid particles is smaller than in distal ileum (~70 µm). Fluid composition in distal ileum is different from cecum, especially in fasted state. CONCLUSION: Differences in luminal environment between distal ileum and cecum may impact the performance of orally administered products which deliver drug during residence in lower intestine. Dosing conditions affect cecal environment more than in distal ileum.