Following drug administration, the initial rapid clearance of the drug from the vascular compartment reflects the distribution of the drug to various tissues. The time it takes to distribute 50% of a drug from the circulation throughout the body is the drug’s distribution half-life (t½). The time required for metabolizing and clearing 50 percent of the drug from the body is the drug’s elimination half-life (t½). The elimination half-life determines the dosing interval.
Assuming first-order kinetics, dosage intervals shorter than the drug’s elimination half-life lead to steady-state concentration (accumulation) of the drug in approximately four half-lives (Figure 10). At steady-state concentration, the rate of drug administration is equal to the rate of drug elimination. Predictably, after the administration of a single dose or the last dose of a drug, it will take approximately four half-lives to eliminate the drug from the body as follows (Figure 10):
Steady-state plasma concentration of a drug may be achieved faster than four half-lives by the administration of an initial loading-dose (LD). By convention, the LD is twice the usual dose. However, when administering a LD caution must be exercised because too high a dose may cause adverse effects. After the administration of an initial LD, the dose recommended to maintain optimal therapeutic levels is defined as the maintenance dose (MD) of the drug.
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