Age-related changes in protein binding of drugs - Implications for therapy

The plasma protein binding of drugs, particularly those that are highly bou nd, may have significant clinical implications. Although protein binding is a major determinant of drug action, it is only one of a myriad of factors that influence drug disposition. The extent of protein binding is a functio n of drug and protein concentrations, the affinity constant for the drug-pr otein interaction and the number of protein binding sites per class of bind ing site. Age-related changes in protein binding are usually not clinically important in drug therapy. Albumin levels are generally decreased in the elderly, wh ereas alpha(1)-acid glycoprotein levels are not altered by age per se. Alte rations in plasma protein binding that occur in the elderly are generally n ot attributed to age, but rather to physiological and pathophysiological ch anges or disease states that may occur more frequently in the elderly and m ost often account for altered protein binding. Age-related physiological ch anges, such as decreased renal function, decreased hepatic function and dec reased cardiac output, generally produce more clinically significant altera tions in drug disposition than that seen with alterations in drug plasma pr otein binding. An understanding of the inter-relationships between drug concentrations, pr otein binding, the physiology of aging, disease, pharmacokinetics and pharm acodynamics is necessary for effective therapeutic monitoring. Monitoring o f unbound drug concentrations simplifies these relationships and provides t he fundamental information needed for dosage regimen development and adjust ment. Drug therapy in the elderly should be individualised taking into acco unt all of these factors.