Cecal Permeability of Salicylic Acid, Halofuginone, and Paraherquamide in the 7-14 Day Old Chicken
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There is a great need for new drugs, with new modes of action to combat coccidiosis-a condition caused by infection of the intestinal tract of livestock by protozoa parasites of the genus Eimeria. However, during the testing of new experimental anti-coccidials, most compounds that show in vitro activity against coccidia, do not show in vitro activity against these organisms. It has been proposed that the poor in vivo activity of these drugs may be due to poor permeability of the cecum--paired sacs that protrude from the intestinal tract of chickens-which is the site of one of the most severe species of coccidia, Eimeria tenella. In this study, three compounds, salicylic acid, halofuginone and paraherquamide were used to study the permeability of the cecum in 7-14 day old chicks under a variety of pH conditions. Permeability of the cecum was quantified as the effective permeability coefficient (P e) and delineated into two components, permeability of the aqueous boundary layer surrounding the tissue (P ABL) and permeability of the tissue itself (P tissue). P tissue was further broken down into the permeability of the aqueous paracellular pathway (Pp) and the lipoidal transcellular pathway (Pm). Using side-by-side diffusion cell systems and the model permeant salicylic acid, the cecum P ABL was shown to be 3 x 10 -4 cm/sec, Pp was 6 x 10-5 cm/sec, and Pm was 14-S x 10-Scm/sec. The effective permeability coefficients of halofuginone (weak acid) and paraherquamide (weak base) were dependent upon pH as expected for weakly acidic and basic molecules which permeate membranes by passive diffusion across the lipoidal transcellular and aqueous paracellular pathways. The ceca is readily permeable to lipophilic drugs. Therefore, it is concluded that the poor in vivo activity of experimental anticoccidials are attributed to factors unrelated to the permeability of the cecum.