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

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.

Characteristics of Contents of Lower intestine in the 65-74 Years of Age Range Could Impact the Performance of Safe and Efficacious Modified Release Products.

We characterized the contents of distal ileum and proximal colon of older people from a pharmaceutical product performance perspective, under two extreme situations, i.e. 5 h after a glass of water to fasted volunteers (fasted state) and 5 h after a high-calorie, high-fat meal to fasted volunteers (fed state). Five males and three females (65-70 y) participated in a two-phase crossover study. Contents were collected via colonoscopy. In distal ileum, luminal pH was lower and buffer capacity was higher than in young adults; differences reached significance for pH in the fed state. In proximal colon, differences reached significance for pH/fasted state and for buffer capacity/both fasted and fed states. Aqueous fraction of contents contained more short chain fatty acids than previously observed in young adults. In distal ileum, osmolality was significantly higher than in young adults. In proximal colon, aqueous fraction in the fasted state was significantly lower and long chain fatty acids 5 h after meal was significantly higher than in young adults. Characteristics of contents of lower intestine that are relevant to the performance of certain modified release products differ between individuals 65-74 years old and young adults, the typical age group employed in safety and efficacy studies of oral drug products.