Pharmacokinetic–Pharmacodynamic Relationship: Dose to Pharmacological Effect

A drug’s dosage and pharmacokinetic properties influence the onset, intensity, and duration of its pharmacologic actions.

Higher drug dosage increases its receptor site concentration, yielding a hyperbolic curve when plotting pharmacologic response versus drug dose.

Here, changing to a log-linear scale results in the sigmoidal curve. For one-compartment model drugs, the pharmacologic response is proportional to log drug plasma concentration.

The effect, E, of drug concentration, C, is expressed as follows, which is solved for providing log C.

However, the post-IV dosing drug concentration is calculated differently, and mathematical substitutions yield another equation indicating the slope km/2.3.

Notably, the slope reflects the linear decline of the pharmacologic response over time. A drug with a higher m value requires frequent dosing to overcome rapidly declining responses.

For example, after the IV administration of lysergic acid diethylamide in healthy human subjects, the log concentration and the performance score, a measure of pharmacologic effect, decline linearly with time.