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Half-Life

Half-life (t1/2) is the time required for serum concentrations to decrease by one-half after absorption and distribution are complete. It takes the same amount of time for serum concentrations to drop from 200 to 100 mg/L as it does for concentrations to decline from 2 to 1 mg/L (Fig. 8–3).

Pharmacotherapy: A Pathophysiologic Approach, 8e > Section 1. Foundation Issues > Chapter 8. Clinical Pharmacokinetics and Pharmacodynamics > Clinical Pharmacokinetic Concepts > Half-Life >


Half-life is important because it determines the time required to reach steady state and the dosage interval. It takes approximately three to five half-lives to reach steady-state concentrations during continuous dosing. In three half-lives, serum concentrations are at 90% of their ultimate steady-state values. Because most serum drug assays have an 10% error, it is difficult to differentiate concentrations that are within 10% of each other. For this reason, many clinicians consider concentrations obtained after three half-lives to be Css.
Half-life is also used to determine the dosage interval for a drug. For instance, it may be desirable to maintain maximum steady-state concentrations at 20 mg/L and minimum steady-state concentrations at 10 mg/L. In this case, it would be necessary to administer the drug every half-life because the minimum desirable concentration is one-half the maximum desirable concentration.
Half-life is a dependent kinetic variable because its value depends on the values of CL and VD.8 The equation that describes the relationship among the three variables is t1/2 = 0.693VD/CL. Changes in t1/2 can result from a change in either VD or CL; a change in t1/2 does not necessarily indicate that CL has changed. Half-life can change solely because of changes in VD. The elimination rate constant (k) is related to the half-life by the following equation: k = 0.693/t1/2. Both the half-life and elimination rate constant describe how quickly serum concentrations decrease in the serum or blood.

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