Biology of frailty: Implications for clinical pharmacology and drug therapy in frail older people

Abstract

Polypharmacy is very common in frail older people, although medications are rarely evaluated in this population. We conducted a narrative review of the effects of the biology of frailty on clinical pharmacology to inform the extrapolation of the results from clinical trials in robust people to the treatment of frail older people. Biological changes of frailty, such as changes in body composition, organ function and vulnerability to external stressors, are likely to impact on the pharmacokinetics and pharmacodynamics of drugs when used in frail older people. We considered whether these theoretical impacts were observed in the limited empirical data on pharmacokinetics in frail and robust older people. We applied what is known about the biology of frailty to interpret results of clinical trials that have conducted subgroup analyses of drug response by frailty status; and results of observational data on the safety of medications when used in frail older people. Synthesising the effects of the biology of frailty on clinical pharmacology is complicated by the use of different definitions of frailty, including a range of validated scales (that identify different people as frail), clinical judgement and residence in a nursing home.

Keywords: Clinical pharmacology; Frail; Pharmacodynamics; Pharmacokinetics; Polypharmacy.