Clinical Pharmacokinetic Considerations in the Elderly. An Update

There are numerous studies of drug handling in the elderly, but it is difficult to assess the significance of changes seen in vitro, or after single-dose administration, because they are often compensated by other mechanisms at steady-state. However, a knowledge of these studies is important as the results alert the investigator to possible treatment problems. The high incidence of adverse drug reaction in the elderly population leaves no doubt that improvements in therapy are needed. Research has been directed at seeking patterns of abnormality in the elderly on which to base recommendations for alterations in dosage regimens. The major shortcoming of this approach has been the failure to distinguish between the effect of chronological age on drug pharmacokinetics, and drug kinetics in elderly people with multiple pathology. The latter concern appreciates the variety of factors involved and the importance of treating each patient as an individual: presentation of mean data is confusing and misleading. The objective of drug treatment in any age group, but particularly in the elderly, is to administer the smallest possible dose which gives adequate therapeutic benefit throughout the entire dosage interval with the minimum of side effects. For most drugs the safe starting dose in the elderly is one-third to half that recommended in the young. Vigilance for potential side effects with plasma concentration monitoring, if available, should help keep toxicity to a minimum. When other medications are added or changed, the possibility of interaction should be anticipated. Methods for individualisation of dosage regimens and the use of sustained-release formulations in the elderly are discussed. Dosage alteration in the elderly in terms of reduced dose frequency, rather than dose size, may help improve compliance. A knowledge of the pharmacokinetics of a drug helps determine which approach will be most beneficial.