Pharmacokinetic Consequences of Aging

For the purpose of this review we have chosen a rather narrow definition of geriatric pharmacology. We deal with the influence of increasing age on the plasma concen­ tration of a drug and the factors that influence the peak concentration and the rate at which the drug leaves the body. We also discuss what changes in tissue sensitivity occur with age that would affect the overall response to a drug at a given blood level concentration. We do not discuss the extensive literature on the safety and utility of drugs in geriatric patients or the effect of increasing age on the incidence of adverse reactions and altered drug utility. Reviews on these have been published ( 1-5). Not considered as part of this review is one other aspect of geriatric phar­ macology, namely, the effect of drugs on the aging process. Information on this aspect of the subject can be found in other reviews (6,7). We would like to remark on the progress that has been made in our understanding of the effects of age on how a drug is handled by the body and the implications that these changes have on the utility of pharmacological agents in the treatment of diseases of old age. Until recently, most of the work has concerned the use of drugs in the elderly patient to determine their safety and their efficacy. There have been few comparisons with the response in younger populations. Even when such com­ parisons have been made, however, there have been few attempts to explain the reason for these differences and the basic biological rationale for them. In the last several years, however, greater attention has been focused on the effect of age on mechanisms responsible for drug disposition, and we are gradually laying the foun­ dation for understanding how drugs may be more effectively used in the treatment of diseases of the elderly patient (813). It is our hope that the review of this biological rationale, and more specifically the pharmacokinetic aspects of increasing age, will contribute to this understanding.