Figure 3-11 The relationship between changes in protein concentration and changes in free fraction depends on the free fraction in normal plasma with typical clinical doses. For a drug that is not bound (free fraction ≅ 1), there is no change in free fraction with a change in protein concentration. For a highly bound drug with a free fraction that is nearly 0, any change in protein causes a nearly inversely proportional change in free fraction. (Adapted from Shafer S: Principles of pharmacokinetics and pharmacodynamics. In Longnecker DE, Tinker JH, Morgan GE [eds]: Principles and Practice of Anesthesiology, 2nd ed. St. Louis, Mosby-Year Book, 1997.)