A MODIFIED RESIDUAL METHOD TO ESTIMATE THE ZERO-ORDER ABSORPTION RATE-CONSTANT IN A ONE-COMPARTMENT MODEL

The objective of this work was to develop a simple residual method to estimate the rate constant for actual or apparent zero-order absorptio n into a one-compartment model. The method is based on the fact that, in theory, a plot of residuals versus e(-Kt) is linear for a zero-orde r absorption process, where K represents the elimination rate constant governing the terminal phase of the concentration-time profile. The a pparent absorption rate constant (K-0) can be calculated from the slop e and intercept of the residual plot. Simulated concentration-time dat a with superimposed random error (CV = 5, 10, 15%, n = 8), as well as data sets from the literature for hydroflumethiazide and theophylline were analyzed with the proposed method of residuals. Parameters derive d with the new technique were compared to both the nonlinear least-squ ares regression and the Wagner-Nelson method, all of which yield compa rable K-0 estimates. These results indicate that the proposed method o f residuals represents a simple approach for estimating the apparent z ero-order absorption rate constant analogous to classic residual analy sis for first-order absorption. (C) 1997 by John Wiley & Sons, Ltd.