Pharmacokinetic–Pharmacodynamic Relationship: Duration of Dose-Effect Relationship

For drugs producing a quantal response, onset occurs when plasma concentration reaches a minimum effective level (C_min). The drug's action duration depends on how long the plasma concentration remains above C_min.

Two primary factors influence this duration: dose size and the rate of drug removal from the action site. Both depend on the drug's redistribution to poorly perfused tissues and elimination processes. A larger dose promotes rapid onset and prolongs the effect's duration.

Consider a rapidly distributing drug administered as an intravenous bolus dose. Eventually, the plasma concentration falls below which the drug elicits no response. This time defines the drug's duration of effect. This duration is also a function of the drug's half-life; in the elimination phase, each dose doubling increases the duration by approximately one half-life, provided the concentration remains well above C_min. However, this approach can be harmful for drugs with a narrow therapeutic index. An alternative is administering the same dose when the drug level drops to C_min, resulting in a minimal increase in duration.

These observations provide valuable insights into optimizing drug dosing strategies, particularly for drugs with narrow therapeutic indices, thereby improving patient outcomes.