The Wagner Nelson Method

A major shortcoming of the method of residuals for determining the absorption rate constant from plasma concentration versus time data following administration of oral solid dosage forms is the necessity to assume that the absorption process obeys first-order kinetics. Although this assumption is often valid for solutions and rapidly dissolving dosage forms for which the absorption process itself is rate determining, if release of drug from the dosage form is rate determining, the kinetics are often zero-order, mixed zero-and first-order, or even more complex processes.

The Wagner-Nelson method of calculation does not require a model assumption concerning the absorption process. It does require the assumption that (i) the body behaves as a single homogeneous compartment and (ii) drug elimination obeys first-order kinetics. The working equations for this calculation are developed next.

Derivation. For any extravascular drug administration, the mass balance equation can be written as amount absorbed (A) equals amount in body (W) plus amount eliminated (E), or

Taking the derivative with respect to time yields dA dt dW dE dt dt

But and

Therefore,

On rearranging we have

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