The impact of advancing age on P-glycoprotein expression and activity: current knowledge and future directions

With the progressive ageing of the population, an increasing number of elderly patients are being exposed to multiple drugs because of co-existing morbidity states requiring pharmacological management. However, the knowledge of the effects of ageing on the pharmacokinetics and pharmacodynamics of individual drugs is far from being optimal as very few elderly subjects are studied in Phase I and II premarketing trials. The efflux transporter P-glycoprotein has recently emerged as a major determinant of drug disposition in humans. This review discusses the current knowledge about the effects of advancing age on P-glycoprotein expression and activity. A critical appraisal of the published literature and an overview on future research directions are also provided.