Increases in half-life caused by disease and age or drug interactions will significantly effect serum drug levels and may produce toxicity in patients if the amount of the dose and the dosing schedule is not appropriately modified. At steady-state the amount of drug being eliminated from the body is equal to the amount administered. Loading doses circumvent the necessity of waiting three to five half-lives to achieve a maximum therapeutic effect. The dosing interval and the biologic half-life determine the extent of drug accumulation. As seen from Figure 3, patients receiving a drug at a dosing interval longer than the half-life of the drug will exhibit large fluctuations between the peak and trough levels.
Shorter intervals lead to less variation.
To be effective the serum concentration must be maintained within the therapeutic range for the drug. The therapeutic range is defined as the range of serum drug concentrations associated with the desired therapeutic effect and a low risk of toxicity in the majority of patients. Some patients may require serum levels exceeding the upper limit and some below the lower limit to realize optimum benefit from the drug. The therapeutic range should be viewed only as a guide to establishing the appropriate serum concentration for each patient. Drug levels obtained before steady-state has been achieved could be interpreted improperly as being subtherapeutic and prompt an increase in dosage.