TIME multiples of elimination t12

FIGURE 1-4 Fundamental pharmacokinetic relationships for repeated administration of drugs. The blue line is the pattern of drug accumulation during repeated administration of a drug at intervals equal to its elimination t1/2 when drug absorption is 10 times as rapid as elimination.

As the rate of absorption increases, the concentration maxima approach 2 and the minima approach 1 during the steady state. The black line depicts the pattern during administration of equivalent dosage by continuous intravenous infusion. Curves are based on the one-compartment model. Average concentration (Css) when the steady state is attained during intermittent drug administration is

where F is fractional bioavailability of the dose and T is dosage interval (time). By substitution of infusion rate for F • dose/T, the formula is equivalent to Equation (1-2) and provides the concentration maintained at steady state during continuous intravenous infusion.

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