Clearance Models: Compartment Models

Clearance directly measures drug elimination from the central compartment, which comprises plasma and highly perfused organs like kidneys and liver.

Clearance calculations vary depending on the pharmacokinetic models and the administration route.

The one-compartment model describes the pharmacokinetics of polar drugs, such as aminoglycoside antibiotics, given intravenously and excreted readily in urine.

Here, the product of terminal rate constant,  λ_z and total volume of distribution, V_ss gives clearance.

If an oral drug's absorption is faster than its elimination, the terminal rate constant represents elimination. However, in the flip-flop phenomenon, when oral absorption is slower than elimination, the rate constant reflects absorption instead.

The two-compartment model accurately represents the pharmacokinetics of less polar drugs distributed into a poorly blood-perfused compartment. Clinically, the pharmacokinetics of the antibiotic vancomycin are effectively predicted by this model.

Notably, distributional clearance reflects clearance between two compartments: the central, including plasma and well-perfused organs, and the peripheral, housing less-perfused organs.