COMPARTMENT MODEL TO DESCRIBE PERIPHERAL ARTERIAL-VENOUS DRUG CONCENTRATION GRADIENTS WITH DRUG ELIMINATION FROM THE VENOUS SAMPLING COMPARTMENT

The central compartment of an n-compartment mammillary model was concatenated with a gradient compartment (i.e., venous sampling compartment) and with a conventional effect compartment to model arterial-venous drug concentration gradients and the arterial drug concentration vs effect relationship, respectively. To model drug metabolism during transit between the peripheral arterial and peripheral venous circulations, the gradient compartment included a first-order elimination path. Simulations of the model were employed to demonstrate the impact of sampling site (e.g., arterial vs peripheral venous) on analyses of the concentration vs effect relationship.