Mechanistic Fluid Transport Model to Estimate Gastrointestinal Fluid Volume and Its Dynamic Change Over Time
Mechanistic Fluid Transport Model to Estimate Gastrointestinal Fluid Volume and Its Dynamic Change Over Time
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DOI：
10.1208/s12248-017-0145-x
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发表时间：
2017-11-01
期刊：
影响因子：
4.5
通讯作者：
Sun, Duxin
中科院分区：
文献类型：
--
作者：
Yu, Alex;Jackson, Trachette;Sun, Duxin
胃肠道液体容量及其动态变化是研究药物崩解、溶出、转运和吸收的重要内容。然而，关于局部体积及其吸收、分泌和转运的关键问题仍然没有答案。提出了基于磁共振成像（MRI）定量液体体积的动态液体室吸收和转运（DFCAT）模型来估计体内GI体积和GI液体转运。使用人胃肠道中的酚红GI局部浓度验证该模型，该浓度在口服非吸收性酚红后通过人胃肠道插管研究直接测量。测得的局部胃肠道酚红浓度范围为0.05 - 168 μ g/mL（胃）、563 μ g/mL（十二指肠）、202 μ g/mL（近端空肠）和478 μ g/mL（远端空肠）。DFCAT模型表征了观察到的MRI液体体积及其在胃中从275至46.5 mL（从0至30 min）的动态变化，其中粘液层体积为40 mL。30个小肠隔室的体积特征为最大值为14.98 mL，最小值为0.26 mL（0-120 min），每个隔室的粘液层体积为5 mL。0 - 120 min内，近端小肠的局部液体体积范围为5.6 - 20.38 mL，远端小肠为36.4 - 44.08 mL，全小肠为42 - 64.46 mL。DFCAT模型可以应用于预测药物在人体胃肠道中的溶出和吸收，并具有未来的改进。
Gastrointestinal (GI) fluid volume and its dynamic change are integral to study drug disintegration, dissolution, transit, and absorption. However, key questions regarding the local volume and its absorption, secretion, and transit remain unanswered. The dynamic fluid compartment absorption and transit (DFCAT) model is proposed to estimate in vivo GI volume and GI fluid transport based on magnetic resonance imaging (MRI) quantified fluid volume. The model was validated using GI local concentration of phenol red in human GI tract, which was directly measured by human GI intubation study after oral dosing of non-absorbable phenol red. The measured local GI concentration of phenol red ranged from 0.05 to 168 mu g/mL (stomach), to 563 mu g/mL (duodenum), to 202 mu g/mL (proximal jejunum), and to 478 mu g/mL (distal jejunum). The DFCAT model characterized observed MRI fluid volume and its dynamic changes from 275 to 46.5 mL in stomach (from 0 to 30 min) with mucus layer volume of 40 mL. The volumes of the 30 small intestine compartments were characterized by a max of 14.98 mL to a min of 0.26 mL (0-120 min) and a mucus layer volume of 5 mL per compartment. Regional fluid volumes over 0 to 120 min ranged from 5.6 to 20.38 mL in the proximal small intestine, 36.4 to 44.08 mL in distal small intestine, and from 42 to 64.46 mL in total small intestine. The DFCAT model can be applied to predict drug dissolution and absorption in the human GI tract with future improvements.