Effects of variation in drug elimination on five methods for assessing zero-order drug absorption rates.

The area function method for assessing zero-order (ko) drug absorption rates was compared to four other methods under conditions where variation occurs in the plasma concentration data and in the elimination rate constant (kel or k10) for one- or two-compartment models. For deviant kel values of a one-compartment model, the most accurate recovery of ko occurred with the area function method and nonlinear least-squares regression, followed by the Wagner-Nelson and moment analysis methods. With deviant k10 values for a two-compartment model, the order of superiority of the methods was: area function approximately nonlinear regression greater than Loo-Riegelman greater than moment analysis. Moment analysis should generally be reserved for use as an estimation rather than calculation technique. The area function procedure offers particular advantages in ease of data analysis and accuracy of recovered parameters.