BIOPHYSICAL MODEL OF THE TRANSCUTICULAR EXCRETION OF ORGANIC-ACIDS, CUTICLE PH AND BUFFER CAPACITY IN GASTROINTESTINAL NEMATODES

A biophysical model was developed, using Ascaris suum as a model gastr ointestinal nematode, to provide quantitative perspectives into the mi croenvironmental pH within the water-filled, porous, negatively charge d cuticle matrix of gastrointestinal nematodes. The central features o f the model include (a) the constant rate of excretion of organic acid metabolites across the cuticle, (b) the relationship between cuticle pH and pK(a) of the organic acids that determines the fraction of unio nized and ionized species, and (c) the concentration gradient, mean co ncentration and buffer capacity within the cuticle that maintain the c uticle pH. The model may be used to predict the extent to which transc uticular absorption of weakly basic and acidic anthelmintics will be a ffected by transcuticular excretion of organic acid metabolites. Coupl ed with established models for drug absorption by nematodes and the ho st gastrointestinal tract, the cuticle pH model provides new insights to the design of drugs with physicochemical properties that favor abso rption by nematodes.