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 (k ₀) has been developed. The procedure evolves from the convolution integral and requires individual oral-dose plasma concentration 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 for 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.