Characterization of the human upper gastrointestinal contents under conditions simulating bioavailability/bioequivalence studies
Characterization of the human upper gastrointestinal contents under conditions simulating bioavailability/bioequivalence studies
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DOI：
10.1007/s11095-005-8476-1
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发表时间：
2006-01-01
影响因子：
3.7
通讯作者：
Reppas, C
中科院分区：
文献类型：
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作者：
Kalantzi, L;Goumas, K;Reppas, C
目的。本研究旨在比较禁食和进食状态下人体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接受250毫升水或500毫升Enure Plus(R)(一种完全的营养饮料)，并根据位置/液体组合的不同从胃窦或十二指肠抽吸样本长达3.5小时。对样品进行聚乙二醇、pH、缓冲容量、渗透压的分析。表面张力、胃酶、总碳水化合物、总蛋白含量和胆盐。给药后，胃液pH升高，缓冲容量在14~28 mmoL L~(-1)Delta pH(-1)之间(vs.7~18 mmolL~(-1)Delta pH(-1))，胃内容物高渗，胃蛋白酶水平增加一倍，表面张力比加水前低30%。十二指肠餐后和餐前的pH值相似，但餐后缓慢下降至5.2，而缓冲容量从空腹的5.6 mm ol L-1 Delta pH(-1)增加到18-30 mm ol L-1 Delta pH(-1)(p<；0.05)。餐后十二指肠表面张力下降30%，胆盐水平升高2~4倍，肠腔内容物高渗，证实有多肽和糖的存在。这项工作表明，除了已经很好地表征的参数(例如，pH和胆盐水平)之外，缓冲容量、表面张力、渗透压等方面的显著差异。并在餐前/餐后观察食物成分。这些差异应该反映在试验介质中，以预测食物对剂型腔内性能的影响。
Purpose. 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(R) (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(R) administration, gastric pH was elevated, buffer capacity ranged from 14 to 28 mmoL L-1 Delta pH(-1) (vs. 7-18 mmol L-1 Delta pH(-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 Delta pH(-1) (fasted) to 18-30 mmol L-1 Delta pH(-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.