Distribution in the Body proceeds rapidly, because the absorbing surface is greatly enlarged due to the formation of the epithelial brush border (submicroscopic foldings of the plasmalemma). The absorbability of a drug is characterized by the absorption quotient, that is, the amount absorbed divided by the amount in the gut available for absorption. In the respiratory tract, cilia-bearing epithelial cells are also joined on the luminal side by zonulae occludentes, so that the bronchial space and the interstitium are separated by a continuous phospholipid barrier. With sublingual or buccal application, a drug encounters the non-keratinized, multilayered squamous epithelium of the. | 22 Distribution in the Body External Barriers of the Body Prior to its uptake into the blood . during absorption a drug has to overcome barriers that demarcate the body from its surroundings . separate the internal milieu from the external milieu. These boundaries are formed by the skin and mucous membranes. When absorption takes place in the gut enteral absorption the intestinal epithelium is the barrier. This singlelayered epithelium is made up of ente-rocytes and mucus-producing goblet cells. On their luminal side these cells are joined together by zonulae occlu-dentes indicated by black dots in the inset bottom left . A zonula occludens or tight junction is a region in which the phospholipid membranes of two cells establish close contact and become joined via integral membrane proteins semicircular inset left center . The region of fusion surrounds each cell like a ring so that neighboring cells are welded together in a continuous belt. In this manner an unbroken phospholipid layer is formed yellow area in the schematic drawing bottom left and acts as a continuous barrier between the two spaces separated by the cell layer - in the case of the gut the intestinal lumen dark blue and the interstitial space light blue . The efficiency with which such a barrier restricts exchange of substances can be increased by arranging these occluding junctions in multiple arrays as for instance in the endothelium of cerebral blood vessels. The connecting proteins connexins furthermore serve to restrict mixing of other functional membrane proteins ion pumps ion channels that occupy specific areas of the cell membrane. This phospholipid bilayer represents the intestinal mucosa-blood barrier that a drug must cross during its enteral absorption. Eligible drugs are those whose physicochemical properties allow permeation through the lipophilic membrane interior yellow or that are subject to a special carrier transport mechanism. Absorption of such drugs proceeds rapidly because
