Changes in the concentration of plasma proteins will influence the effect of a highly bound drug.
A low plasma protein level may occur in old age or malnutrition. It may also be caused by illness such as liver disease (remember that most plasma proteins are made in the liver), or chronic renal failure where there is excessive excretion of albumin.
In each case the result is a smaller proportion of drug in bound form and more free drug in the plasma. The greater amount of free drug is able to produce a greater therapeutic effect and reduced drug dosages may be indicated in these cases.