Figure 4. Model of antidiarrheal efficacy of a membrane-permeant inhibitor. Computations done for human mid-jejunal crypt–villus anatomy. (A) Schematic showing inhibitor permeation across enterocytes from blood into the crypt–villus lumen, which depends on inhibitor transepithelial permeability coefficient, Pinh, and blood concentration Cb. (B) Steady-state inhibitor concentration profiles for indicated Pinh for Jvo = 2 × 10−2 µL/cm2/s (left), and for indicated Jvo for Pinh = 10−5 cm/s (right), both for Cb = 10 µM and Kd = 10 µM. (C) Percent inhibition of net secreted fluid as a function of Pinh for indicated Jvo at Cb = 10 µM and Kd = 10 µM. (D) Same as in C, with Cb = 1 µM and Kd = 0.1 µM.
Figure 4.

Model of antidiarrheal efficacy of a membrane-permeant inhibitor. Computations done for human mid-jejunal crypt–villus anatomy. (A) Schematic showing inhibitor permeation across enterocytes from blood into the crypt–villus lumen, which depends on inhibitor transepithelial permeability coefficient, Pinh, and blood concentration Cb. (B) Steady-state inhibitor concentration profiles for indicated Pinh for Jvo = 2 × 10−2 µL/cm2/s (left), and for indicated Jvo for Pinh = 10−5 cm/s (right), both for Cb = 10 µM and Kd = 10 µM. (C) Percent inhibition of net secreted fluid as a function of Pinh for indicated Jvo at Cb = 10 µM and Kd = 10 µM. (D) Same as in C, with Cb = 1 µM and Kd = 0.1 µM.

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