Comparison of the gastrointestinal anatomy, physiology, and biochemistry of humans and commonly used laboratory animals.
In addition to metabolic differences, the anatomical, physiological, and biochemical differences in the gastrointestinal (G.I.) tract of the human and common laboratory animals can cause significant variation in drug absorption from the oral route. Among the physiological factors, pH, bile, pancreatic juice, and mucus and fluid volume and content can modify dissolution rates, solubility, transit times, and membrane transport of drug molecules. The microbial content of the G.I. tract can significantly affect the reductive metabolism and enterohepatic circulation of drugs and colonic delivery of formulations. The transit time of dosage forms can be significantly different between species due to different dimensions and propulsive activities of the G.I. tract. The lipid/protein composition of the enterocyte membrane along the G.I. tract can alter binding and passive, active, and carrier-mediated transport of drugs. The location and number of Peyer's patches can also be important in the absorption of large molecules and particulate matter. While small animals, rats, mice, guinea pigs, and rabbits, are most suitable for determining the mechanism of drug absorption and bioavailability values from powder or solution formulations, larger animals, dogs, pigs, and monkeys, are used to assess absorption from formulations. The understanding of physiological, anatomical, and biochemical differences between the G.I. tracts of different animal species can lead to the selection of the correct animal model to mimic the bioavailability of compounds in the human. This article reviews the anatomical, physiological, and biochemical differences between the G.I. tracts of humans and commonly used laboratory animals.
G. D. Searle & Co., Skokie, IL 60077, USA.
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Kararli
D000818:Animals; D000830:Animals, Laboratory; D001646:Bile / Q000378:metabolism; D002415:Cats; D006224:Cricetinae; D004064:Digestive System / Q000033:anatomy & histology* / Q000378:metabolism / Q000382:microbiology; D004068:Digestive System Physiological Phenomena; D004285:Dogs; D005769:Gastrointestinal Motility / Q000502:physiology; D005772:Gastrointestinal Transit / Q000502:physiology; D006736:Horses; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007408:Intestinal Absorption / Q000502:physiology; D050356:Lipid Metabolism; D051379:Mice; D008871:Microvilli / Q000378:metabolism; D009077:Mucins / Q000378:metabolism; D010581:Peyer's Patches / Q000378:metabolism; D011817:Rabbits; D051381:Rats; D013045:Species Specificity; D013552:Swine
D009077:Mucins