A computational gastrointestinal model to predict age and disease effects on oral medications

Oral absorption is determined in healthy adults without considering effects of age or disease on this crucial parameter in therapeutic treatments. To date, in vitro models have been developed mimicking the healthy intestinal fluid.

However, little efforts have been directed to computational assessment of age or disease effects on solubility and absorption.

We have shown that the healthy adult population can be well described in a virtual setting, allowing studies of drug solubilisation and dosage form performance at a molecular level. To take a patient-centered approach, different age and disease groups need to be included.

The goal of this project is therefore to develop validated computational tools suitable for prediction of age and disease effects on solubility and absorption of oral medicines.

We will study intestinal fluid compositions of healthy children and elderly, neonates, and patients suffering from Alzheimer´s Disease and Parkinson´s Disease.

Absorption is studied by enclosing the luminal composition in a virtual intestinal tube composed of model lipid membranes of the enterocytes.

The luminal compositions are based on in vivo data and the simulations are validated through state-of-the-art in vitro methods. Our models lay a platform for in silico assessment of medicines commonly used by specific patient groups.

Importantly, the strategy developed here paves the way for models of other diseases and are not limited to the patient groups studies herein.