Pharmacokinetic dosage guidelines for elderly subjects

Ageing is associated with a decline in drug elimination; hence, using the same doses as in younger adults may result in higher plasma drug concentrations and toxicity. Two approaches are available for dose correction to account for decreased drug elimination. One procedure is based on the extrarenal elimination fraction (Q(0)) and the age-dependent changes in creatinine clearance; the other uses the decline in total drug clearance (CL). Mean values of Q(0) and CL in young and old people are reported for many drugs in the literature and are summarised in this article. Although the pharmacokinetic techniques for dose adjustment in the elderly are useful, they provide only an average dose correction and neglect age-dependent changes in drug bio-availability, plasma protein binding, the fate of active metabolites, and altered sensitivity to drugs. To account for pharmacodynamic changes in old age, clinical and/or biochemical targets should be defined as therapeutic goals. Drugs whose effects cannot be monitored in these terms should be avoided in elderly individuals.