Characterization of the human upper gastrointestinal contents under conditions simulating bioavailability/bioequivalence studies.
OBJECTIVE
This study was conducted to compare the luminal composition of the upper gastrointestinal tract in the fasted and fed states in humans, with a view toward designing in vitro studies to explain/predict food effects on dosage form performance.


METHODS
Twenty healthy human subjects received 250 mL water or 500 mL Ensure plus (a complete nutrient drink) through a nasogastric tube and samples were aspirated from the gastric antrum or duodenum for a period up to 3.5 h, depending on location/fluid combination. Samples were analyzed for polyethylene glycol, pH, buffer capacity, osmolality, surface tension, pepsin, total carbohydrates, total protein content, and bile salts.


RESULTS
Following Ensure plus administration, gastric pH was elevated, buffer capacity ranged from 14 to 28 mmoL L-1 DeltapH-1 (vs. 7-18 mmol L-1 DeltapH-1), contents were hyperosmolar, gastric pepsin levels doubled, and surface tension was 30% lower than after administration of water. Post- and preprandial duodenal pH values were initially similar, but slowly decreased to 5.2 postprandially, whereas buffer capacity increased from 5.6 mmol L-1 DeltapH-1 (fasted) to 18-30 mmol L-1 DeltapH-1 (p<0.05). Postprandial surface tension in the duodenum decreased by >30%, bile salt levels were two to four times higher, luminal contents were hyperosmotic, and the presence of peptides and sugars was confirmed.


CONCLUSIONS
This work shows that, in addition to already well characterized parameters (e.g., pH, and bile salt levels), significant differences in buffer capacity, surface tension, osmolality, and food components are observed pre-/postprandially. These differences should be reflected in test media to predict food effects on intralumenal performance of dosage forms.
Kalantzi
Lida
L
Laboratory of Biopharmaceutics and Pharmacokinetics, School of Pharmacy, University of Athens, Panepistimiopolis, 157 71, Zografou, Greece. reppas@pharm.uoa.gr
Goumas
Konstantinos
K
Kalioras
Vasilios
V
Abrahamsson
Bertil
B
Dressman
Jennifer B
JB
Reppas
Christos
C
D000328:Adult; D001647:Bile Acids and Salts / Q000737:chemistry; D001682:Biological Availability; D002021:Buffers; D004040:Dietary Carbohydrates / Q000032:analysis; D004044:Dietary Proteins / Q000032:analysis; D004386:Duodenum / Q000737:chemistry*; D004435:Eating / Q000502:physiology; D005215:Fasting / Q000378:metabolism; D005260:Female; D005526:Food, Formulated; D005766:Gastrointestinal Contents / Q000737:chemistry*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007441:Intubation, Gastrointestinal; D008297:Male; D009994:Osmolar Concentration; D010434:Pepsin A / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D013500:Surface Tension; D013810:Therapeutic Equivalency; D014867:Water
D001647:Bile Acids and Salts; D002021:Buffers; D004040:Dietary Carbohydrates; D004044:Dietary Proteins; D014867:Water; D011092:Polyethylene Glycols; D010434:Pepsin A