6.15 : Clearance Models: Noncompartmental Models

Clearance is a pharmacokinetic parameter traditionally defined by compartment models, signifying the rate at which a drug is expelled from the body. However, a noncompartmental model offers an alternative method for assessing clearance, primarily employing empirical data obtained after administering a single drug dose.

The noncompartmental approach capitalizes on extensive sampling data, correlating the volume of distribution to systemic exposure and the administered dosage. This method enables the robust computation of clearance without any presuppositions. In this context, clearance depends on bioavailability, the dosage of the drug, and the area under the concentration-time curve (AUC).

The AUC serves as an indicator of total systemic exposure following a single dose administration. Calculating the observed AUC from time zero to t or the last detectable concentration is accomplished using the trapezoidal rule, which is extrapolated to infinity.

In a steady-state scenario, the quantity of drug administered equals the amount eliminated over a given dosing interval. Meanwhile, the clearance formula incorporates a constant dosing rate and steady-state concentration during a steady-state intravenous infusion.