Half-life (t1/2) is the time required to change the amount of drug in the body by one-half during elimination (or during a constant infusion).

Half-life (*t*1/2) is the time required to change the amount of drug in the body by one-half during elimination (or during a constant infusion). In the simplest case—and the most useful in designing drug dosage regimens—the body may be considered as a single compartment (as illustrated in Figure 3–2B) of a size equal to the volume of distribution (V). The time course of drug in the body will depend on both the volume of distribution and the clearance:

Because drug elimination can be described by an exponential process, the time taken for a twofold decrease can be shown to be proportional to the natural logarithm of 2. The constant 0.7 in equation (6) is an approximation to the natural logarithm of 2.

Half-life is useful because it indicates the time required to attain 50% of steady state—or to decay 50% from steady-state conditions—after a change in the rate of drug administration. Figure 3–3 shows the time course of drug accumulation during a constant-rate drug infusion and the time course of drug elimina-tion after stopping an infusion that has reached steady state.

Disease states can affect both of the physiologically related primary pharmacokinetic parameters: volume of distribution and clearance. A change in half-life will not necessarily reflect a change in drug elimination. For example, patients with chronic renal failure have decreased renal clearance of digoxin but also a decreased volume of distribution; the increase in digoxin half-life is not as great as might be expected based on the change in renal function. The decrease in volume of distribution is due to the decreased renal and skeletal muscle mass and consequent decreased tissue binding of digoxin to Na+/K+-ATPase.

Many drugs will exhibit multicompartment pharmacokinetics (as illustrated in Figures 3–2C and 3–2D). Under these condi-tions, the “true” terminal half-life, as given in Table 3–1, will be greater than that calculated from equation (6)

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Basic & Clinical Pharmacology : Pharmacokinetics & Pharmacodynamics: Rational Dosing & the Time Course of Drug Action : Half-Life - Pharmacokinetics |

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