Wagner-Nelson method

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

In the development of equations for the Wagner-Nelson method of calculation, the following equation was derived [see Eq. (42)] ... 

As the clearance of rhG-CSF is known to decrease with a rise in dose and is known to be saturable, the average clearance after i.v. administration will be lower than that after s.c. administration. Therefore, the apparent absolute bioavailability with subcutaneous administration calculated from the AUC ratio is expected to be a conservative estimate. In a second study by Flayashi et al., the estimation of rhG-CSF absorption kinetics after s.c. administration with a nonlinear elimination pharmacokinetic model using a modified Wagner-Nelson method was studied... 

Hayashi N, Aso H, Higashida M, et al. (2001). Estimation of rhG-CSF absorption kinetics after subcutaneous administration using a modified Wagner-Nelson method with a nonlinear elimination model. Eur. J. Pharmaceu. Sci. 13 151-158. 

Percentage absorbed plot (Wagner-Nelson method) from plasma or urinary data... 

The absorption curves can be calculated by various methods as stated by the FDA estimate the in vivo absorption or dissolution time course using an appropriate deconvolution technique for each formulation and subject (e.g., Wagner-Nelson, numerical deconvolution). The usual techniques are presented in Table After... 

The most commonly used model-dependent deconvolution methods for estimating the apparent in vivo drug absorption following oral administration are the Wagner-Nelson (5) method and the Loo-Riegelman method (6). These methods depend on mass balance and the fraction of drug absorbed for a one-compartment model is expressed as... 

The absorption rate constant obtained by the feathering, or residual, method could be erroneous under the conditions stated above. Should that be the case, it is advisable to employ some other methods (Wagner and Nelson method, statistical moment analysis, Loo-Rigelman method for a two-compartment model, just to mention a few) of determining the absorption rate constant. Though these methods tend to be highly... 

We remain cognizant that this edition of the textbook includes some references that may be considered by some viewers not to be the most current. We, however, believe that the chosen references are classic ones best suited to illustrate a particular point. Additionally, we fully recognize that this edition omits topics such as the Wagner and Nelson method for the determination of the absorption rate constant, urinary data analysis following the administration of a drug by an extravascular route, two-compartment model pharmacokinetics for an extravascularly administered dmg, and metabolite kinetics. 

Two other methods have been described that require modelling of the disposition pharmacokinetics but not of the absorption phase. For drugs with disposition pharmacokinetics that can be approximated by a one-compartment model, i.e., the declining part of the plasma concentration-time curve can be approximated by a one log-linear phase, the following equation can be applied to determine the fractional amount absorbed (A) at different times t after administration (Wagner and Nelson 1963) ... 

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