Pharmacodynamic Models: Linear Concentration–Effect Model

The linear concentration–effect model, underpinned by the principle that pharmacological effect (E) is directly proportional to plasma drug concentration (C), emerges as a pivotal simplification of the E_max model for conditions where C is significantly less than EC₅₀. This model portrays a linear trajectory of the concentration–effect relationship when drug levels are markedly below the EC₅₀ threshold.

Despite its inherent assumption of continuous effect augmentation with increasing drug concentrations up to a maximal effect (E_max), the model acknowledges the practical limitations of its linearity across extensive concentration ranges. As a result, it confines its applicability to comprehensive pharmacodynamic modeling. However, its utility is exemplified in the precise evaluation of drug-induced cardiac repolarization effects, as measured by the QT interval on electrocardiograms. It has been extensively applied in characterizing the concentration-QTc relationship for moxifloxacin and developing new pharmacological entities.

The concentration-QTc analysis facilitates the US FDA's regulatory review processes, particularly in assessing the proarrhythmic risks associated with novel therapeutic agents, underscoring its significance in advancing drug safety evaluations.