The time it takes for the amount of compound in the body to decrease to one half of the original amount is the half-life (see Fig. 1.4). Half-life is expressed in units of time (i.e., hours). Halflife can be calculated as follows:
For a 2-compartment model (see Sect. 1.3)
The degree of accumulation following multiple doses is governed by the half-life/elimination rate constant. The Accumulation ratio R is defined as follows:
Cmax or where
Cmax is the highest or peak blood/plasma concentration after a single dose
Cmax(ss) is Cmax at steady state
T (tau) is the dosing interval in units of time (i.e., hours)
Half-life is related to volume of distribution and CL as follows:
An increase in volume of distribution or a decrease in CL will cause an increase in half-life.
Estimation of the terminal half-life is sometimes influenced by the sensitivity of the bioanalytical assay. In cases where there is inadequate sensitivity and/or low doses are administered, the terminal phase is not adequately characterized resulting in a much shorter than actual half-life estimate.
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