Clearance measures drug elimination from the central compartment, including plasma and highly perfused organs like kidneys and liver. Its calculation varies depending on pharmacokinetic models and administration routes. The one-compartment model, for instance, portrays the pharmacokinetics of polar drugs such as aminoglycoside antibiotics administered intravenously and readily excreted in urine. In this case, clearance is influenced by the terminal rate constant (λ_z) and the total volume of distribution (V_ss). If absorption is quicker than elimination for oral drugs, the terminal rate constant signifies elimination. Conversely, if absorption is slower, the rate constant indicates absorption.

The two-compartment model effectively represents the pharmacokinetics of less polar drugs distributed into a poorly blood-perfused compartment. This model accurately predicts the pharmacokinetics of the antibiotic vancomycin (Vancocin). Distributional clearance denotes clearance between two compartments: the central compartment, encompassing plasma and well-perfused organs, and the peripheral compartment, housing less-perfused organs.

Understanding these models and factors will help optimize drug dosing and minimize potential side effects.