CLINICAL PHARMACOLOGY OF AGE, SEX AND FRAILTY: INSIGHTS FROM CLINICAL AND POPULATION STUDIES

This presentation will discuss areas of agreement and disagreement, and identify gaps in knowledge of age, sex and frailty-related effects on drug clearance and responses. Agreement exists that renal clearance decreases with age, sex and possibly frailty, yet, there remains disagreement about the best way to estimate renal drug clearance to adjust medication doses in older people and in frail vs. non-frail. For oxidative CYP-mediated drug clearance, consistent decreases have been seen with aging in vitro and in vivo yet results from clinical populations do not detect consistent effects. Human data on age and frailty effects on transporters to guide dosing in clinical populations have yet to emerge. Evidence for a prominent role of polypharmacy in medication problems seen in clinical populations will be discussed as well as the altered pharmacodynamics reserve associated with older age and/or frailty that may underlie altered responses to medications.