Guerra Aurélie, Denis Sylvain, le Goff Olivier, Sicardi Vincent, François Olivier, Yao Anne-Françoise, Garrait Ghislain, Manzi Aimé Pacifique, Beyssac Eric, Alric Monique, Blanquet-Diot Stéphanie
EA 4678 Conception, Ingénierie et Développement de l'Aliment et du Médicament Clermont Université, Université d'Auvergne, Centre de Recherche en Nutrition Humaine Auvergne, Faculté de Pharmacie, 28 Place H. Dunant, F-63001, Clermont-Ferrand, France.
Protolab, Clermont Ferrand, France.
Biotechnol Bioeng. 2016 Jun;113(6):1325-35. doi: 10.1002/bit.25890. Epub 2015 Dec 10.
For ethical, regulatory, and economic reasons, in vitro human digestion models are increasingly used as an alternative to in vivo assays. This study aims to present the new Engineered Stomach and small INtestine (ESIN) model and its validation for pharmaceutical applications. This dynamic computer-controlled system reproduces, according to in vivo data, the complex physiology of the human stomach and small intestine, including pH, transit times, chyme mixing, digestive secretions, and passive absorption of digestion products. Its innovative design allows a progressive meal intake and the differential gastric emptying of solids and liquids. The pharmaceutical behavior of two model drugs (paracetamol immediate release form and theophylline sustained release tablet) was studied in ESIN during liquid digestion. The results were compared to those found with a classical compendial method (paddle apparatus) and in human volunteers. Paracetamol and theophylline tablets showed similar absorption profiles in ESIN and in healthy subjects. For theophylline, a level A in vitro-in vivo correlation could be established between the results obtained in ESIN and in humans. Interestingly, using a pharmaceutical basket, the swelling and erosion of the theophylline sustained release form was followed during transit throughout ESIN. ESIN emerges as a relevant tool for pharmaceutical studies but once further validated may find many other applications in nutritional, toxicological, and microbiological fields. Biotechnol. Bioeng. 2016;113: 1325-1335. © 2015 Wiley Periodicals, Inc.
出于伦理、监管和经济方面的原因，体外人体消化模型越来越多地被用作体内试验的替代方法。本研究旨在介绍新型工程化胃和小肠（ESIN）模型及其在药物应用方面的验证。这个动态的计算机控制系统根据体内数据再现了人类胃和小肠的复杂生理过程，包括pH值、转运时间、食糜混合、消化液分泌以及消化产物的被动吸收。其创新设计允许逐步进食以及固体和液体的不同胃排空情况。在液体消化过程中，在ESIN中研究了两种模型药物（对乙酰氨基酚速释剂型和茶碱缓释片）的药物行为。将结果与经典药典方法（桨法装置）以及人类志愿者的结果进行了比较。对乙酰氨基酚和茶碱片在ESIN和健康受试者中显示出相似的吸收曲线。对于茶碱，在ESIN和人体中获得的结果之间可以建立A级体外-体内相关性。有趣的是，使用药物篮，在整个ESIN转运过程中跟踪了茶碱缓释剂型的溶胀和侵蚀情况。ESIN成为药物研究的一个相关工具，但一旦进一步验证，可能会在营养、毒理学和微生物学领域找到许多其他应用。生物技术与生物工程。2016年；113：1325 - 1335。©2015威利期刊公司。
