Age-related pharmacokinetic and pharmacodynamic changes and related risk of adverse drug reactions.

Aging is known to be associated with an increased prevalence of multiple chronic diseases, which frequently causes the use of complex therapeutic regimens. The aging process is characterized by relevant changes in drug handling, physiological reserve, and pharmacodynamic response. Hepatic drug clearance of several drugs decreases with aging, mainly due to reduced blood flow, and hepatocyte mass. Renal function also declines with aging, mainly due to sclerotic changes in the glomeruli. Furthermore, due to reduced muscle mass, older subjects frequently have depressed glomerular filtration rate despite normal serum creatinine, and such a concealed renal insufficiency may impact significantly the clearance of hydrosoluble drugs. Changes in pharmacodynamics are also well documented in the cardiovascular and nervous system. Age-related changes in pharmacokinetics and pharmacodynamics, together with comorbidity and polypharmacy, make elderly patients at special risk for adverse drug reactions, which in turn are cause of relevant health burden and costs. Selected measures can assist in preventing or detecting timely such adverse events.