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Abstract
Physiologic changes and disease-related alterations in organ function occur with aging.
These changes can affect drug pharmacokinetics in older persons.
This article reviews age-related changes in pharmacokinetics and their clinical relevance.
A PubMed search was conducted using the terms elderly and pharmacokinetics. Other
reviews were also included for literature searching. The review includes literature
in particular from 1990 through April 2004. Some articles from before 1990 were included
to help illustrate principles of age-related pharmacokinetics.
There are minor changes in drug absorption with aging. The effect of aging on small-bowel
transporter systems is not yet fully established. Bioavailability of highly extracted
drugs often is increased with age. Transdermal absorption may be delayed, especially
in the case of water-soluble compounds. Fat-soluble drugs may distribute more widely
and water-soluble drugs less extensively in older persons. Hepatic drug metabolism
shows wide interindividual variation, and in many cases, there is an age-related decline
in elimination of metabolized drugs, particularly those eliminated by the cytochrome
enzyme system. Any decrement in cytochrome enzyme metabolism appears nonselective.
Synthetic conjugation metabolism is less affected by age. Pseudocapillarization of
the sinusoidal endothelium in the liver, restricting oxygen diffusion, and the decline
in liver size and liver blood flow may influence age-related changes in rate of hepatic
metabolism. Frailty, physiological stress, and illness are important predictors of
drug metabolism in older individuals. Inhibition of drug metabolism is not altered
with aging, but induction is reduced in a minority of studies. Renal drug elimination
typically declines with age, commensurate with the fall in creatinine clearance. Renal
tubular organic acid transport may decline with age, while the function of the organic
base transporter is preserved but may be less responsive to stimulation.
Changes in pharmacokinetics occur due to age-related physiologic perturbations. These
changes contribute to altered dose requirements in older persons, particularly in
the case of drugs eliminated by the kidney. Interindividual variation, disease, frailty,
and stress may overshadow age-related changes.