The area function method for assessing the drug absorption rate in linear systems with zero-order input

Abstract

A noncompartmental approach for determination of the apparent zero-order absorption rate constant (k0) has been developed. The procedure evolves from the convolution integral and requires individual oral-dose plasma concentrations values and calculation of area intervals under the plasma concentration-time curves after intravenous administration. The proposed method was evaluated and compared with the Wagner-Nelson, Loo-Riegelman, deconvolution, nonlinear regression, and moment methods using errorless and errant simulation data from one- or two-compartment models. The area function method is generally equal to the best of these techniques (nonlinear regression) and superior to the weaker methods (moment, deconvolution, Loo-Riegelman), especially for errant two-compartment data. Coupled with a companion procedure for constructing fraction absorbed versus time plots and assessing first-order absorption rate constants, the area function methods offer direct and accurate means of discerning drug absorption kinetics without the need for assignment of a disposition model for drugs with linear elimination kinetics.