Clearance is a key pharmacokinetic parameter that quantifies the volume of body fluid from which a drug is entirely removed within a specific time frame. It is crucial in assessing how a drug is eliminated from the body and has critical clinical applications.
In the one-compartment open model for intravenous (IV) bolus administration, clearance is estimated by dividing the elimination rate by the plasma drug concentration. This equation leverages the elimination rate constant and the apparent volume of distribution to estimate clearance. Total body clearance is the cumulative clearance by all eliminating organs, whereas total systemic clearance is the aggregate of individual organ clearances, illustrating how the body processes the drug.
Hepatic clearance, which evaluates drug elimination by the liver is estimated by dividing the elimination rate by the drug concentration presented to the liver. It can be further categorized into hepatic blood flow rate-limited clearance and intrinsic capacity-limited clearance. Drug clearance in the kidneys and other organs can be estimated similarly by dividing the elimination rate by the drug concentration presented to the kidneys and other organs respectively.
Several methods, including the method of residuals, can be used to calculate clearance. This technique separates a multiexponential curve into its components. By analyzing plasma concentration-time profiles and applying suitable equations, we can estimate clearance to understand drug elimination from the body.
From Chapter 7:
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