Evaluating the impact of advanced age and age-related diseases on gastrointestinal drug behaviour and on the biochemical barrier of the intestinal mucosa

The absorption of drugs from oral dosage forms is largely controlled by drug dissolution in the gastrointestinal contents and drug permeation through the intestinal epithelium. However, the influence of age and age-related diseases on these processes is poorly understood. The overall goal of this project is to generate information on drug and formulation behaviour in older people and geriatric patients, and on physiological characteristics of their gastrointestinal tract relevant to oral drug absorption. More specifically, the impact of advanced age and of Alzheimer’s disease will be explored. Effects on dissolution-related processes will be evaluated by sampling and characterizing gastrointestinal fluids. Effects on drug permeation will be assessed by collecting intestinal tissue samples and determining the protein abundancy of transporters and metabolizing enzymes relevant for drug disposition (mass spectrometry-based proteomics). As such, unique reference data will be generated on gastrointestinal physiology and drug behaviour in older people with or without Alzheimer’s disease. These data will contribute to the development of population specific PBPK models to predict drug absorption, thereby supporting the efficient development and use of oral drug products tailored to these fragile patients.

Keywords:pharmacokinetics, pharmacometrics, PBPK modelling, drug permeation, drug disposition, proteomics, mass-spectometry

Disciplines:Drug discovery and development not elsewhere classified

Project type:PhD project