The aging process is different for everyone, and hence the population of persons over 65 is very diverse. Persons belonging to this group often have multiple illnesses and multiple regimens of medication, which along with their advanced age can lead to changes of the gastrointestinal tract. Whether these subsequent changes can affect the oral drug therapy thereby warrants investigation. For example, is a physiological change in the stomach more important than that in the lower intestine? To what degree does such a change affect absorption and is the effect positive or negative?  It is important to understand how such factors influence drug therapy, to identify risks and subsequently minimize them. To do this, specialized computer simulations can be used to predict absorption by combining knowledge of human physiology and of the drug. Together with powerful analytical techniques, it is possible to control the analysis to provide answers to the previous questions and more in a manner that is reproducible and takes less time than using other methods.  As shown in the image, data points represent real people, some of which may be more vulnerable to these age-associated changes than others. Therefore, modelling and simulations are important to ensure safe and effective therapies for patients.

The aging process is different for everyone, leading to high inter-individual variability in the population over 65 years. Physiological changes of the gastrointestinal tract, increasing patterns of comorbidities, and high rates of polypharmacy are all associated with advanced age. Whether these subsequent changes can affect the oral absorption and therapeutic efficacy of drugs thereby warrants investigation. Physiologically based Pharmacokinetic/Biopharmaceutic Models may be used to predict absorption by combining knowledge of the physiology and drug physico-chemistry and formulation, however this leads to highly dimensional models with many correlated parameters. As can be seen in the image, even 3 dimensions or factors can produce convoluted perspectives and relationships between parameters may not be easily detected. For this reason, a variety of computational techniques, particularly Global Sensitivity Analyses have been explored to identify and quantify the effects of age-associated changes on oral absorption of drugs. As shown in the image, data points represent real people, some of which may be more vulnerable to these age-associated changes than others. Therefore, testing and proper choice of method is important to balance the computational costs, intrinsic limitations, and accuracy of the results. Using such techniques it is possible to discern, which factors are driving deviations in absorption in special populations, so that they may be taken into account in early drug development, leading to safe medications for everyone.