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, a value of zero is used.
The value of AUCINF (AUC¥) may be user-specified or compute as for non-compartmental analysis:
AUC¥=AUClast+Clast/Lambda_z
Either the observed or predicted value for Clast, where Clast_pred=exp(intercept – Lambda_z*tlast) can be used. Several methods for computing Lambda Z are available: best fit, user-specified range, or user-specified intercept value. If the intercept is not specified, it will be computed using the last positive concentration and associated time value:
intercept=Lambda_z*tlast+ln(Clast)
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)
Therefore, Cumul_Amt_Abs_V at t=infinity is:
Cumul_Amt_Abs_V(inf)=Lambda_z*AUC¥
The relative fraction absorbed at time t is then:
Rel_Fraction_Abs(t)=Cumul_Amt_Abs_V(t)/Cumul_Amt_Abs_V(inf)
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.
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