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Updated: May 2, 2026
10:22
In Vitro and In Vivo Approaches to Determine Intestinal Epithelial Cell Permeability
Published on: October 19, 2018
25.4K
Predicting the Peritoneal Absorption of Icodextrin in Rats and Humans Including the Effect of α-Amylase Activity in
Alp Akonur1, Clifford J Holmes2, John K Leypoldt2
1Medical Products R&D (Innovation), Baxter Healthcare Corporation, One Baxter Parkway, Deerfield, IL 60015, USA.
Summary
This study modified a three-pore model to predict icodextrin absorption and ultrafiltration, accounting for amylase degradation. The model accurately predicted increased absorption and ultrafiltration, especially in rats, due to amylase activity in peritoneal dialysis fluid.
Area of Science:
- Peritoneal Dialysis
- Mathematical Modeling
- Pharmacokinetics
Background:
- Icodextrin absorption from peritoneal dialysis fluid is complex.
- Previous models struggled to incorporate α-amylase degradation of icodextrin.
- A modified three-pore model was developed to address these limitations.
Purpose of the Study:
- To predict icodextrin absorption and ultrafiltration simultaneously.
- To incorporate the effect of α-amylase degradation in peritoneal transport models.
- To validate the modified model in both rat and human subjects.
Main Methods:
- Developed separate three-pore models for rats and humans.
- Incorporated first-order kinetics for icodextrin degradation by α-amylase.
- Simulated 4-hour exchanges in rats and 9/14-hour exchanges in humans.
- Accounted for different patient transport characteristics (slow vs. fast).
Main Results:
- In rats, amylase activity significantly increased ultrafiltration (21.1%) and icodextrin absorption (7.1%).
- In humans, the shift in molecular weight profile was less pronounced.
- Amylase activity increased ultrafiltration by 15% and absorption by 1.5% in humans during 14-hour exchanges.
- Fast transporters absorbed more icodextrin than slow transporters.
Conclusions:
- The modified three-pore model accurately predicts icodextrin absorption and ultrafiltration.
- Amylase activity in dialysate increases ultrafiltration due to generated small molecules.
- The effect of amylase is more pronounced in rats than humans due to higher enzyme concentrations.
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