The relationship of protein binding to overall clinical effect is complex in nature. Half-life is essential for determining the appropriate dosing interval of a medication. Steady state is reached when the amount of drug administered equals the amount of drug eliminated. It is achieved within four to five half-lives of a drug. As a general rule of thumb, the dosing interval of a medication should be at least two to three times the half-life.
Clearance is the intrinsic ability of the body to remove a drug.
In general, clearance is inversely proportional to age in children. The initial dosing regimen can then be tailored to conform to an individual patient's drug disposition characteristics. Most clinicians are familiar with the use of peak serum concentrations to monitor efficacy. For example, a neonate who becomes tachycardic after each theophylline dose but then does well throughout the rest of the dosing interval may have a peak concentration above the therapeutic range. Lowering the peak by giving a smaller dose more frequently may result in the same reduction in apneic episodes without the periods of tachycardia.