Characterization of the contents of ascending colon to which drugs are exposed after oral administration to healthy adults.
OBJECTIVE
To characterize the contents of the ascending colon in healthy adults under fasting and fed state conditions, with a view to designing in vitro studies to explain/predict dosage form performance in the lower gut.


METHODS
Twelve healthy adults participated in a two-phase crossover study. In Phase A, subjects were fasted (water allowed) overnight plus 5 h in the morning prior to colonoscopy (fasted state). In Phase B, subjects were fasted overnight, consumed a standard breakfast (960 kcal) in the morning, and were offered a light lunch 4.5 h later. In this phase, colonoscopy was performed 1 h after lunch (fed state). Volume, pH, and buffer capacity of colonic contents were measured immediately upon collection. After ultracentrifugation, the supernatant was further characterized.


RESULTS
Free water content, pH, surface tension, and isobutyrate levels were lower in fed than in fasted subjects. On the other hand, buffer capacity, osmolality, acetate, butyrate, cholate, and chenodeoxycholate levels were higher in fed subjects. Carbohydrate content; protein content; and levels of long chain fatty acids, phosphatidylcholine, and cholesterol were not affected significantly by prandial state.


CONCLUSIONS
Composition of fluids in the ascending colon is affected by feeding. This may affect the performance of products designed to deliver drug to the colon.
Diakidou
Amalia
A
Faculty of Pharmacy, Laboratory of Biopharmaceutics and Pharmacokinetics, National & Kapodistrian University of Athens, Panepistimiopolis, Zografou, Greece.
Vertzoni
Maria
M
Goumas
Konstantinos
K
Söderlind
Erik
E
Abrahamsson
Bertil
B
Dressman
Jennifer
J
Reppas
Christos
C
D000284:Administration, Oral; D000328:Adult; D044682:Colon, Ascending / Q000187:drug effects*; D018592:Cross-Over Studies; D006801:Humans; D006863:Hydrogen-Ion Concentration; D010600:Pharmacology; D010865:Pilot Projects; D012016:Reference Values