Drug dosage in the elderly. Is it rational?

Pharmacotherapy in the elderly requires an understanding of the age-dependent changes in function and composition of the body. Aging is characterised by a progressive loss of functional capacities of most if not all organs, a reduction in response to receptor stimulation and homeostatic mechanisms, and a loss of water content and an increase of fat content in the body. The most important pharmacokinetic change in old age is a decrease in the excretory capacity of the kidney; in this regard, the elderly should be considered as renally insufficient patients. The decline in the rate of drug metabolism with advancing age is less marked. In addition, the volume of distribution and the oral bioavailability of drugs may be changed in the elderly compared with younger individuals. Average dosage adjustments for the aged can be derived from simple equations and mean pharmacokinetic parameters from older and younger adults. However, these average dose adjustment factors neglect the large variation in the decline in organ functions among the elderly. Individual dose adjustment factors can be obtained from the drug clearance in a particular patient, where clearance/fractional bioavailability (CL/f) may be calculated from the area under the plasma concentration-time curve (AUC) of the drug in question. Using pharmacokinetic guidelines for dose adjustments, the same plasma drug concentrations result in elderly as in younger adults. However, we are frequently confronted with pharmacodynamic changes in old age which alter the sensitivity to drugs, irrespective of changes in drug disposition. For instance, the sensitivity of the cardiovascular system to beta-adrenergic agonists and antagonists decreases in old age and the incidence of orthostatic episodes in response to drugs that lower blood pressure is increased. The CNS is especially vulnerable in the elderly; agents that affect brain function (anaesthetics, opioids, anticonvulsants, psychotropic drugs) must be used very cautiously in this age group. The increased responsiveness to drugs in the elderly renders the measurement of drug plasma concentrations an attractive method to monitor pharmacotherapy in this age group. Sensitive technology to quantitatively determine plasma drug concentrations is available. However, optimal therapeutic plasma concentrations have not been established for most drugs in the elderly. Investigations concerning drug pharmacokinetic-pharmacodynamic relationships in the aged are an important area of future work in clinical pharmacology.