Gastrointestinal physiology and drug disposition in geriatric patients

Gastrointestinal factors such as pH and transit times are important determinants for drug absorption. Age-related motility and pH changes, but also malnutrition and the use of specific drug classes are assumed to influence these GI factors. These factors are highly prevalent in geriatric patients. Hence, we will investigate the influence of the former on pH and transit times by means of clinical studies using the Smartpill or salivary tracer techniques. The data will further be used in in vitro tools and PBPK modelling in order to predict the effect on oral drug absorption in older patients in collaboration with Abbvie and the consortium. Objectives: 1) Assess the effect of (i) advanced age, (ii) malnutrition and (iii) the intake of neuroleptics and anticholinergics on transit times, gastric fluid emptying and pH in geriatric patients; 2) Assess the relevance of these effects on oral drug absorption by applying the in vivo data in (i) biorelevant in vitro tools and (ii) PBPK modelling. Expected Results: new knowledge on the effect of frequently used drugs and malnutrition (common in older age) on transit times and GI pH levels. The project will provide reference data to improve in vitro tools and PBPK modelling.