Drug Dosing

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):

  • After 1 half-life 50% of the drug is remaining in the body and 50% has been eliminated
  • After 2 half-lives 25% of the drug is remaining in the body and 75% has been eliminated
  • After 3 half-lives 12.5% of the drug is remaining in the body and 87.5% has been eliminated
  • After 4 half-lives 6.25% of the drug is remaining in the body and 93.75% has been eliminated
Figure 10.
effect of dosing on plasma concentrations
The effect of dosing on plasma concentrations.

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.