Purpose: Map the luminal environment in the distal ileum and in the cecum of the elderly by measuring physical and chemical characteristics relevant to drug / drug product performance under fasting and fed state conditions and compare with previously reported data in adults.
Methods: Contents of the distal ileum and caecum were collected during colonoscopy. Eight volunteers (65-71y) participated in a two-phase study on a crossover basis, after receiving approvals by the Scientific and the Executive Committee of the Red Cross Hospital (AP 167 - 016 June 2016). Subject work-up consisted of administration of 20 mg of bisacodyl 50-44 h prior to colonoscopy. Subjects were fasted overnight prior to colonoscopy day. In Phase 1 (fasted state) on colonoscopy day subjects continue to fast from food (but not from water) until 12 noon when collection of contents of distal ileum and of cecum was performed (anaerobically, through the colonoscope). In Phase 2 (fed state) on colonoscopy day subjects consumed a standard breakfast (960 kcal) at 08:00 and water-only until 13:00 when collection of contents of lower intestine was performed as in Phase 1.
Volume, pH, and buffer capacity of contents were measured immediately upon collection. The rest of the sample was ultracentrifuged anaerobically, the % aqueous portion was measured and the supernatant was kept at -70 °C until further analyses were performed. Osmolarity, total bile content and short chain fatty acids were determined in all supernatants.
Results: In distal ileum, median values in the fasted vs. fed state were as follows:
Compared with previous data in adults (Reppas et al. Pharm. Res. 32:3338-3349 (2015) the following significant differences were detected:
- in distal ileum, the total volume of contents is lower, osmolarity is higher in the fasted state, pH is lower in the fed state and concentration of total short chain fatty acids is higher in the fed state.
- in cecum, buffer capacity and short chain fatty acid content are higher, pH and % liquid content are lower in the fasted state and osmolality is higher in the fasted state.
Conclusion: Differences in luminal environment between elderly and adults may impact the performance of orally administered products which deliver the drug in the lower intestine. For example, the performance of a colon targeting product which relies primarily on the “high pH values in the lower intestine” may be problematic in the elderly.
Authors would like to thank Ms Maria Koursari (Red Cross Hospital of Athens) for superb technical assistance during the colonoscopies.
Sarah Soulaiman– National and Kapodistrian University of Athens, Athens
Konstantinos Goumas– Director of Department of Gastroenterology, Red Cross Hospital of Athens, Athens
Elisabeth Kersten– Lab Head Early Formulation Development, Bayer AG, Wuppertal
Uwe Muenster– Laborleiter/in, Bayer AG
Christos Reppas– Professor of Pharmaceutics, National and Kapodistrian University of Athens, Athens