Intestinal absorption by carrier-mediated transports: two-dimensional laminar flow model

Area of Science:

• Pharmacokinetics
• Biophysical Chemistry
• Physiology

Background:

• Carrier-mediated transport is crucial for intestinal drug and biological substance absorption.
• The unstirred water layer (UWL) can significantly influence apparent kinetic parameters.
• Accurate determination of kinetic parameters is essential for predicting absorption.

Purpose of the Study:

• To adapt a two-dimensional laminar flow model for analyzing intestinal absorption.
• To investigate the impact of the UWL on Michaelis constant (Km) and maximum transport velocity (Vmax).
• To develop a method for determining true kinetic parameters from experimental data.

Main Methods:

• Adaptation of a two-dimensional laminar flow model for single perfusion experiments.
• Mathematical analysis of carrier-mediated transport kinetics in the presence of UWL.
• Application of Lineweaver-Burk plots to apparent kinetic parameters.

Main Results:

• The apparent Km at the inlet was higher than the true Km at the intestinal wall.
• Lineweaver-Burk plots yielded apparent Km and Vmax values larger than true values.
• Deviations increased with higher Vmax/Km ratios and lower perfusion rates.
• Concurrent passive transport led to underestimation of carrier-mediated transport and Vmax.
• Water absorption or secretion affected absorption rates without saturation.

Conclusions:

• The developed two-dimensional laminar flow model enables accurate determination of true Km and Vmax.
• The model accounts for the confounding effects of the unstirred water layer.
• This approach improves the reliability of kinetic parameter estimation in intestinal absorption studies.