FIG. 4

Effect of a change in protein binding (free fraction, FF) on steady-state plasma concentrations of free (unbound) drug and total (free plus bound) drug. It is assumed that dosing rate and free clearance are constant. Left: Free fraction is 0.1; that is, the drug is 90% bound to plasma protein. The free concentration is 1.0 mg/ml, and the total concentration is 10.0 mg/ml. Right: An intervening factor reduces the extent of plasma protein binding. The free fraction is now 0.2; the drug is 80% bound to protein. Since dosing rate and free clearance are not changed, steady-state free concentration remains at 1.0 mg/ml. However, the total concentration falls to 5.0 mg/ml.

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published 2000