Surface area assessment of the murine intestinal tract as a prerequisite for oral dose translation from mouse to man.
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 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.
Casteleyn
C
C
Department of Morphology, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, Merelbeke, Belgium. Christophe.Casteleyn@ugent.be
Rekecki
A
A
Van der Aa
A
A
Simoens
P
P
Van den Broeck
W
W
D000284:Administration, Oral; D000818:Animals; D004305:Dose-Response Relationship, Drug; D020895:Enterocytes / Q000378:metabolism / Q000648:ultrastructure*; D005260:Female; D006801:Humans; D007408:Intestinal Absorption / Q000502:physiology*; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000033:anatomy & histology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D008871:Microvilli / Q000378:metabolism / Q000648:ultrastructure; D009929:Organ Size; D013045:Species Specificity; D015262:Xenobiotics / Q000493:pharmacokinetics*
D015262:Xenobiotics