Author:

Keywords:

Science & Technology, Life Sciences & Biomedicine, Pharmacology & Pharmacy, PBPK modelling, Absorption, Older people, Elderly, Peroral, In silico, Clinical pharmacology, Oral drug development, GASTRIC-ACID-SECRETION, HELICOBACTER-PYLORI INFECTION, GASTROINTESTINAL TRANSIT, ELDERLY-PATIENTS, FRAILTY INDEX, SERUM GASTRIN, YOUNG-ADULTS, HEALTHY-MEN, FOOD, HIV, Drug Development, Dietary Supplements, Models, Biological, Computer Simulation, absorption, clinical pharmacology, elderly, in silico, older people, oral drug development, peroral, 1115 Pharmacology and Pharmaceutical Sciences, 3214 Pharmacology and pharmaceutical sciences

Abstract:

The older population consisting of persons aged 65 years or older is the fastest-growing population group and also the major consumer of pharmaceutical products. Due to the heterogenous ageing process, this age group shows high interindividual variability in the dose-exposure-response relationship and, thus, a prediction of drug safety and efficacy is challenging. Although physiologically based pharmacokinetic (PBPK) modelling is a well-established tool to inform and confirm drug dosing strategies during drug development for special population groups, age-related changes in absorption are poorly accounted for in current PBPK models. The purpose of this review is to summarise the current state-of-knowledge in terms of physiological changes with increasing age that can influence the oral absorption of dosage forms. The capacity of common PBPK platforms to incorporate these changes and describe the older population is also discussed, as well as the implications of extrinsic factors such as drug-drug interactions associated with polypharmacy on the model development process. The future potential of this field will rely on addressing the gaps identified in this article, which can subsequently supplement in-vitro and in-vivo data for more robust decision-making on the adequacy of the formulation for use in older adults and inform pharmacotherapy.