https://pubmed.ncbi.nlm.nih.gov/37329924/
Eur J Pharm Sci. 2023 Jun 15;106496
Cleo Demeester, Donnia Robins, Angela Elma Edwina, Jos Tournoy, Patrick Augustijns, Ibrahim Ince, Andreas Lehmann, Maria Vertzoni, Jan Frederik Schlender
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 aging 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 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.
Keywords: PBPK modelling; absorption; clinical pharmacology; elderly; in silico; older people; oral drug development; peroral.
https://pubmed.ncbi.nlm.nih.gov/37329924/ Eur J Pharm Sci. 2023 Jun 15;106496 Cleo Demeester, Donnia Robins, Angela Elma Edwina, Jos Tournoy, Patrick Augustijns, Ibrahim Ince, Andreas Lehmann, Maria Vertzoni, Jan Frederik Schlender
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 aging 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 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.
Keywords: PBPK modelling; absorption; clinical pharmacology; elderly; in silico; older people; oral drug development; peroral.
Copyright © 2023. Published by Elsevier B.V.