CLINICAL PHARMACOKINETIC CONSIDERATIONS IN THE ELDERLY - AN UPDATE

There are a number of areas in which advances have been made over the last few years in the area of pharmacokinetics in the elderly. There i s increasing understanding of the diversity of cytochrome P450s (CYP) and the variability of the age-related decline in CYP activity. This h as helped to explain some of the interindividual variability in drug m etabolism with age. The importance of ethnic differences has emerged. but specific work is needed in this area in the elderly. Differences i n the handling of chiral compounds has been reported but as yet no cli nically important findings that may lend to a change in clinical pract ice have emerged. The emerging importance of extrahepatic drug metabol ism, especially in the intestine, has added a new complexity to our un derstanding of pharmacokinetics. The issue of frailty is also discusse d in this article. Whether it will be of value at the bedside has yet to emerge. Nonetheless, as a concept, recent data has supported its po tential use to define those more at risk of clinically meaningful phar macokinetic alterations. Other advances have included the appreciation that selectivity in induction and inhibition in the elderly are due t o the existence of multiple CYP forms. Similarly, the role of these va rious enzymes in disease is also improving our clinical understanding, as exemplified in Parkinson's disease.