For example, under normal circumstances, highly protein-bound drugs such as phenytoin have a relatively constant fraction of free drug, rendering routine free phenytoin levels of little use. In these situations, total phenytoin is adequate for assessing therapeutic effect. Monitoring free phenytoin becomes important, however, when metabolism, excretion, or protein binding is altered. Under these conditions, pharmacological effect may correlate better with free drug concentrations, while the use of therapeutic ranges based on total drug may be invalid. Free drug analysis includes a total drug level, a free level, and a percent free level.
Total drug is used in conjunction with free drug to calculate the percent free drug.
This percentage may then be used to estimate the total drug level that will cause a therapeutic free drug level. Causes decreased drug binding and increased free drug fraction. Persons over 65 tend to have decreased protein concentrations, and so, increased free drug concentration. Any physiologic factor that results in increased protein will decrease the free drug fraction. Any physiologic factor that results in decreased protein will increase the free drug fraction.