Age-related changes in pharmacokinetics: predictability and assessment methods.

Although there have been relatively few studies of the pharmacokinetics of antiepileptic drugs (AEDs) in old age, available evidence indicates that the clearance of most old and new generation AEDs is reduced on average by about 20-40% in elderly patients compared with nonelderly adults. Depending on the pharmacokinetic characteristics of the drug, the reduction in clearance can be ascribed to a physiological reduction in rate of drug metabolism, to a decrease in renal excretion rate, or to both. Studies have consistently demonstrated that interindividual pharmacokinetic variability in old age is particularly prominent, due not only to the influence of aging-related physiological changes, but also to the impact of comorbidities and drug-drug interactions. For extensively metabolized drugs, there are no reliable tools to predict with a high degree of accuracy the pharmacokinetic behavior of an AED in an individual patient. With renally eliminated drugs, determination of creatinine clearance may provide a useful clue in predicting individual changes in drug clearance and the consequent need for dosage adjustment. In the therapeutic setting, measurement of serum AED concentrations can be valuable in individualizing dosage in an elderly person, even though it should be remembered that in the case of drugs that are highly bound to plasma proteins the total serum concentration may underestimate the level of unbound, pharmacologically active drug. Because aging is also associated with important pharmacodynamic changes that may alter the relationship between serum drug concentration and pharmacological effects, pharmacokinetic measurements alone are not a substitute for the need to monitor clinical response carefully and to adjust dosage accordingly.