Persson Eva M, Nilsson Ralf G, Hansson Göran I, Löfgren Lars J, Libäck Fredrik, Knutson Lars, Abrahamsson Bertil, Lennernäs Hans
Department of Pharmacy, Uppsala University, Box 580, S-751 23, Uppsala, Sweden.
Pharm Res. 2006 Apr;23(4):742-51. doi: 10.1007/s11095-006-9607-z. Epub 2006 Feb 22.
To investigate the gastrointestinal secretory and enzymatic responses to a liquid meal during in vivo perfusion of the proximal human jejunum.
Human intestinal fluid was collected from the proximal jejunum by single-pass in vivo perfusion (Loc-I-Gut). The fluid was quantitatively collected at 10-min intervals during 90 min while perfusing a nutritional drink at 2 mL/min. Quantification of lipids in the fluid leaving the segment was performed by using novel chromatographic methods.
The overall bile acid concentration varied between 0.5 and 8.6 mM with a peak level 40 min after the start of the liquid meal perfusion. The total concentration of phospholipids was between 0.1 and 3.9 mM and there was a rapid degradation of phosphatidylcholine to lysophosphatidylcholine. The tri-, di-, monoglycerides and free fatty acid levels increased sharply in the beginning and reached steady-state levels between 7 and 9.5 mM.
There is a rapid secretion of bile in response to food. Most of the dietary lipids are found in the form of their degradation products in vivo in human jejunum. This novel in vivo characterization, based on direct and high-recovery sampling of intestinal fluids, forms a basis for further development of improved in vitro drug dissolution test media.
研究在人体空肠近端进行体内灌注期间,液体餐对胃肠道分泌及酶反应的影响。
通过单通道体内灌注(Loc-I-Gut)从空肠近端收集人体肠液。在以2毫升/分钟的速度灌注营养饮料的90分钟内,每隔10分钟定量收集一次液体。采用新型色谱方法对离开该段的液体中的脂质进行定量分析。
总胆汁酸浓度在0.5至8.6毫摩尔之间变化,在液体餐灌注开始后40分钟达到峰值。磷脂总浓度在0.1至3.9毫摩尔之间,磷脂酰胆碱迅速降解为溶血磷脂酰胆碱。甘油三酯、甘油二酯、甘油单酯和游离脂肪酸水平在开始时急剧上升,在7至9.5毫摩尔之间达到稳态水平。
食物可迅速刺激胆汁分泌。在人体空肠内,大部分膳食脂质以其降解产物的形式存在于体内。这种基于直接且高回收率的肠液采样的新型体内特征分析,为进一步开发改进的体外药物溶出试验介质奠定了基础。