WagnerNelson Object

The WagnerNelson model is a one-compartment IV-bolus model that uses deconvolution to estimate the fraction of drug absorption. The model also generates AUCs (Areas Under the Curve) and rate of absorption values. This deconvolution model is best used to calculate the absorption kinetics of intravenously administered drugs.

For drugs that are administered through methods other than IV-bolus, such as oral or transdermal methods, it is preferable to use the Deconvolution object to evaluate drug release and absorption. For more information on the Deconvolution object, see “Deconvolution”.

Use one of the following to add a WagnerNelson object to a Workflow:

Right-click menu for a Workflow object: New > IVIVC > WagnerNelson
Main menu: Insert > IVIVC > WagnerNelson.
Right-click menu for a worksheet: Send To > IVIVC > WagnerNelson.

Note:To view the object in its own window, select it in the Object Browser and double-click it or press ENTER. All instructions for setting up and execution are the same whether the object is viewed in its own window or in Phoenix view.

This section contains the following topics:

WagnerNelson inputs and calculations

The Wagner-Nelson method estimates the fraction of drug absorbed over time, relative to the total amount to be absorbed, following the method described in Gibaldi and Perrier (1975) pages 130 to 133. It uses as a basis AUC values computed for each time point in the time-concentration data.

Note:Wagner-Nelson computations assume single-dose PK data with a concentration value of zero at dose time. If no concentration value exists at dose time, WinNonlin will insert a concentration value of zero.

The value of AUCINF (AUC_¥) may be user-specified or WinNonlin can compute it as for non-compartmental analysis:

AUC_¥=AUC_last+C_last/Lambda_z

(1)

Either the observed or predicted value for C_last, where C_{last_pred}=exp(intercept – Lambda_z*t_last) can be used. As in the Wagner-Nelson method, the method for computing Lambda Z is specified by the user: best fit, user-specified range, or user-specified value. An intercept for the last case can be entered by the user. If the intercept is not specified, WinNonlin will compute it using the last positive concentration and associated time value:

intercept=Lambda_z*t_last+ln(C_last)

(2)

The cumulative amount absorbed at time t, normalized by the central compartment volume V1, is computed as:

Cumul_Amt_Abs_V(t)=C(t)+Lambda_z*AUC(t)

(3)

Therefore, Cumul_Amt_Abs_V at t=infinity is:

Cumul_Amt_Abs_V(inf)=Lambda_z*AUC_¥

(4)

The relative fraction absorbed at time t is then:

Rel_Fraction_Abs(t)=Cumul_Amt_Abs_V(t)/Cumul_Amt_Abs_V(inf)

(5)

Data points with a missing value for either time or the concentration will be excluded from the analysis and will not appear in the output.