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Permeability Characteristics of Various Intestinal Regions of Rabbit,Dog, and Monkey
Authors:Jezyk  Nancy  Rubas  Werner  Grass  George M.
Affiliation:(1) Institute of Pharmaceutical Sciences, Syntex Research, Palo Alto, California, 94303;(2) Present address: Pharmaceutical Research and Development, Genentech, Inc., 460 Point San Bruno Boulevard, MS 6, South San Francisco, California, 94080;(3) Present address: College of Pharmacy, University of Michigan, Ann Arbor, Michigan, 48109;(4) Precision Instrument Design, P.O. Box 1242, Tahoe City, California, 96145
Abstract:The in vitro permeability of a series of both hydrophilic and lipophilic compounds, as defined by the octanol/water partition coefficient, was measured in four segments of rabbit, monkey, and dog intestine using a side-by-side diffusion cell. A linear relationship was established for tissue resistance to hydrophilic compound diffusion in jejunum and colon among rabbit, monkey, and dog. The results suggest that rabbit jejunum is twice as permeable as monkey and dog jejunum. The colonic tissues of monkey, rabbit, and dog demonstrate similar permeabilities. Measuring the permeabilities of different tissues with compounds of similar physicochemical properties allows comparison of tissue restriction to transport. Thus, in vitro permeability measurements may be used to investigate physiological differences of various intestinal tissue segments that influence tissue permeability. Investigating the permeability of different intestinal segments from various species could allow the identification of an appropriate in vitro intestinal permeability model that will lead to the prediction of intestinal absorption in humans, eliminating the need for extensive and often misleading in vivo animal testing.
Keywords:intestinal permeability  partition coefficient  jejunum  colon  species differences
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