Concentration-time profile for a hypothetical drug administered orally in multiple doses. The drug is administered once every half-life (i.e., every 8 hours). Drug continues to accumulate (i.e., concentrations rise) until steady state (rate in = rate out) is reached at approximately 5 half-lives (about 40 hours).

cating achievement of a steady state of concentration (drug input = drug elimination).

The only practical method for achieving steady-state concentrations prior to five half-lives is to administer a bolus dose of drug (a dose much higher than normal and designed to bring concentrations up to steady state immediately) followed by standard dosing (Figure 5.5). In this way, the "accumulation" of drug occurs rapidly because of the large amount of drug given initially. However, bolus doses must be calculated in accordance with both the drug's pharmacokinetic parameters and the physiological characteristics of the individual to avoid potential toxicities.

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