Biophysical model of the transcuticular excretion of organic acids, cuticle pH and buffer capacity in gastrointestinal nematodes.

Abstract:

:A biophysical model was developed, using Ascaris suum as a model gastrointestinal nematode, to provide quantitative perspectives into the microenvironmental pH within the water-filled, porous, negatively charged cuticle matrix of gastrointestinal nematodes. The central features of the model include (a) the constant rate of excretion of organic acid metabolites across the cuticle, (b) the relationship between cuticle pH and pKa of the organic acids that determines the fraction of unionized and ionized species, and (c) the concentration gradient, mean concentration and buffer capacity within the cuticle that maintain the cuticle pH. The model may be used to predict the extent to which transcuticular absorption of weakly basic and acidic anthelmintics will be affected by transcuticular excretion of organic acid metabolites. Coupled with established models for drug absorption by nematodes and the host gastrointestinal tract, the cuticle pH model provides new insights to the design of drugs with physicochemical properties that favor absorption by nematodes.

journal_name

J Drug Target

authors

Sims SM,Ho NF,Magas LT,Geary TG,Barsuhn CL,Thompson DP

doi

10.3109/10611869409015888

subject

Has Abstract

pub_date

1994-01-01 00:00:00

pages

1-8

issue

1

eissn

1061-186X

issn

1029-2330

journal_volume

2

pub_type

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