“Variability of pharmacokinetic parameters due to age”


Aging is an additional source of variability in drug pharmacokinetics. This age-induced variability is considered for each of the four main pharmacokinetic mechanisms:

  1. Absorption: Drug absorption does not appear to change dramatically with age. Generally, changes in the rate rather than in the extent of absorption are found. As exceptions, marked differences in absorption are observed in the neonatal period and in the elderly. In both cases, a decrease in hepatic metabolism and first pass effect may lead to an increase in oral bioavailability of some drugs.
  2. Distribution: The volume of distribution is frequently directly proportional to body weight and modulated by age. In some cases, age-related changes in drug binding can affect the volume of distribution (e.g. decrease in extracellular fluid in the elderly).
  3. Metabolism: Aging clearly affects metabolism. The enzymes involved in both phase I and phase II metabolism mature gradually following the first two to four weeks following postpartum. Full maturity appears in the second decade of life with a subsequent slow decline in function associated with aging. The overall decrease of metabolic clearance is around 1 % per year.
  4. Excretion: Renal clearance normalized for bodyweight is depressed in neonates but then rapidly increases to reach a maximum at six months. Throughout adulthood, age is associated with an average decrease in renal function of 1% per year. But most strikingly, age is associated to an increase in the variability of renal clearance among individuals.

Clinical implications

Adaptation of drug regimens is most important for neonates, infants and in the elderly. The lack of maturation of renal and hepatic function in the neonates and young infants necessitates that the rate of administration of drugs be reduced. In children, drug clearance is considered to correlate better with body surface area than body weight. Therefore, higher maintenance dose per kilogram body weight are required the smaller and the younger the child.

At the other extreme, drug use in the elderly generally requires significant reductions in drug dose reflecting the general decline in body function with age. Therefore, increase attention should be given to both treatment failure and toxicity. In the elderly, there should be awareness of possible exaggerated pharmacodynamic responses, as there may be a increase in sensitivity of target organs.