Kalantzi Lida, Goumas Konstantinos, Kalioras Vasilios, Abrahamsson Bertil, Dressman Jennifer B, Reppas Christos
Laboratory of Biopharmaceutics and Pharmacokinetics, School of Pharmacy, University of Athens, Panepistimiopolis, 157 71, Zografou, Greece.
Pharm Res. 2006 Jan;23(1):165-76. doi: 10.1007/s11095-005-8476-1. Epub 2006 Dec 1.
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.
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.
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.
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.
本研究旨在比较人类禁食和进食状态下上消化道的管腔成分，以期设计体外研究来解释/预测食物对剂型性能的影响。
20名健康受试者通过鼻胃管摄入250 mL水或500 mL安素益加（一种全营养饮品），根据位置/液体组合，在长达3.5小时的时间内从胃窦或十二指肠抽取样本。分析样本中的聚乙二醇、pH值、缓冲容量、渗透压、表面张力、胃蛋白酶、总碳水化合物、总蛋白含量和胆汁盐。
摄入安素益加后，胃内pH值升高，缓冲容量为14至28 mmol L-1 ΔpH-1（相比之下，摄入水后为7至18 mmol L-1 ΔpH-1），内容物为高渗，胃蛋白酶水平翻倍，表面张力比摄入水后低30%。餐后和餐前十二指肠pH值最初相似，但餐后缓慢降至5.2，而缓冲容量从5.6 mmol L-1 ΔpH-1（禁食）增加至18至30 mmol L-1 ΔpH-1（p<0.05）。十二指肠餐后表面张力下降超过30%，胆汁盐水平高出两至四倍，管腔内容物为高渗，且证实存在肽和糖。
这项研究表明，除了已充分表征的参数（如pH值和胆汁盐水平）外，餐前/餐后缓冲容量、表面张力、渗透压和食物成分存在显著差异。这些差异应在测试介质中体现，以预测食物对剂型管腔内性能的影响。
