Surface area assessment of the murine intestinal tract as a prerequisite for oral dose translation from mouse to man
Surface area assessment of the murine intestinal tract as a prerequisite for oral dose translation from mouse to man
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DOI：
10.1258/la.2009.009112
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发表时间：
2010-07-01
影响因子：
2.4
通讯作者：
Van den Broeck, W.
中科院分区：
文献类型：
--
作者：
Casteleyn, C.;Rekecki, A.;Van den Broeck, W.
在许多药理学和毒理学研究中，关于肠道吸收的知识是必不可少的，肠道吸收取决于吸收上皮的表面积。尽管小鼠经常用于此类临床前研究，但有关其肠道表面积的定量数据却很少。特别是对于正在开发的局部作用候选药物，这些信息对于将剂量转化为人体至关重要。因此，本研究评估了 CD-1 (TM) IGS 小鼠肠道的表面积。安乐死后收集12只小鼠的肠道。根据常见的体视学原理，对六只动物的十二指肠、空肠、回肠、盲肠和结肠直肠进行组织切片。使用这些切片，通过体视计数程序估计每个肠段的体积和表面积。在其他六只动物中，通过扫描和透射电子显微镜测定每个肠段中存在的微绒毛的密度和表面积，以评估由于微绒毛的存在而导致的肠道表面积的增加。肠道的平均总体积和表面积分别为1.34 cm(3) 和1.41 m(2)。相对肠道表面积（肠道表面积除以体表面积）为119。小鼠的相对肠道表面积与人类非常相似。这项研究的结果对于从小鼠到人类的药物开发中候选治疗化合物的适当剂量转换非常重要。
In many pharmacological and toxicological studies knowledge about the intestinal absorption, which is dependent upon the surface area of absorptive epithelia, is indispensible. Although mice are often used in such preclinical studies, very few quantitative data about their intestinal surface area are available. Especially for locally acting candidate drugs in development, this information is crucial for dose translation towards humans. Therefore, the surface area of the intestinal tract of CD-1 (TM) IGS mice was assessed in the present study. The intestinal tracts of 12 mice were collected after euthanasia. From six animals, histological sections from the duodenum, jejunum, ileum, caecum and colon-rectum were made according to common stereological principles. Using these sections, the volumes and surface areas of each intestinal segment were estimated applying stereological counting procedures. In the other six animals, the density and surface area of the microvilli present in each intestinal segment were determined by means of scanning and transmission electron microscopy to assess the increase of the intestinal surface area attributable to the presence of microvilli. The mean total volume and surface area of the intestinal tract were 1.34 cm(3) and 1.41 m(2), respectively. The relative intestinal surface area (intestinal surface area divided by the body surface area) was 119. The relative intestinal surface area of mice is very similar to that of humans. The results of this study are important for the appropriate dose translation of candidate therapeutic compounds in drug development from mouse to humans.