8.7 : Parameters Affecting Nonlinear Elimination: Zero-Order Input, First-Order Absorption and Two-Compartment Model

Drugs administered through different administration routes follow nonlinear elimination.

Consider a drug administered through a constant IV infusion, exemplifying zero-order input and eliminated by nonlinear pharmacokinetics. The following equation describes the rate of change in plasma drug concentration.

For instance, oral drugs are absorbed through first-order absorption and eliminated through nonlinear pharmacokinetics. It can be determined by the following equation.

Certain drugs are administered subcutaneously to get absorbed from the hypodermis site into the blood. These follow a two-compartment model with two elimination processes. A saturable process of receptor-mediated elimination in the bone marrow and a nonsaturable elimination process through the kidneys.

The model can be represented by two differential equations defined by respective Michaelis-Menten parameters.

Clearance of a drug may be considered as two parts. α is the function of dose with no dimensions and can take a value from 0 to 1.