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 is increasing understanding of the diversity of cytochrome P450s (CYP) and the variability of the age-related decline in CYP activity. This has helped to explain some of the interindividual variability in drug metabolism with age. The importance of ethnic differences has emerged, but specific work is needed in this area in the elderly. Differences in the handling of chiral compounds has been reported but as yet no clinically important findings that may lead to a change in clinical practice have emerged. The emerging importance of extrahepatic drug metabolism, especially in the intestine, has added a new complexity to our understanding of pharmacokinetics. The issue of frailty is also discussed 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 potential use to define those more at risk of clinically meaningful pharmacokinetic alterations. Other advances have included the appreciation that selectivity in induction and inhibition in the elderly are due to the existence of multiple CYP forms. Similarly, the role of these various enzymes in disease is also improving our clinical understanding, as exemplified in Parkinson's disease.