Usefulness of monitoring free (unbound) concentrations of therapeutic drugs in patient management.

Drugs are bound to various serum proteins in different degrees and only unbound or free drug is pharmacologically active. Although free drug concentration can be estimated from total concentration, for strongly bound drugs, prediction of free level is not always possible. Conditions like uremia, liver disease and hypoalbuminemia can lead to significant increases in free drug resulting in drug toxicity even if the concentration of total drug is within therapeutic range. Drug-drug interactions may also lead to a disproportionate increase in free drug concentrations. Elderly patients may have increased free drug concentrations due to hypoalbuminemia. Elevated free phenytoin concentrations have also been reported in patients with AIDS and pregnancy. Currently free drug concentrations of anticonvulsants such as phenytoin, carbamazepine and valproic acid are widely measured in clinical laboratories. Newer drugs such as mycophenolic acid mofetil and certain protease inhibitors are also considered as candidates for monitoring free drug concentration.