Effects of Variation in Drug Elimination on Five Methods for Assessing Zero-Order Drug Absorption Rates

The area function method for assessing zero-order (k_o) 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 (k_el or k₁₀) for one- or two-compartment models. For deviant k_el values of a one-compartment model, the most accurate recovery of k_o 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 ≈ nonlinear regression > Loo-Riegelman > 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.