Re: kinetic interpolation and effect compartments

From kgkowa@searle.monsanto.com Tue Sep 24 12:13:48 1996 Subject: Re: kinetic interpolation and effect compartments Rik, You might want to consider the semicompartmental modeling approach that I have been developing. The semicompartmental approach is a solution to Sheiner's effect-site link model based on a noncompartmental model for Cp (piecewise linear or log-linear model) and is easily implemented in standard nonlinear regression packages such as NONLIN, NONMEM, and SAS NLIN. I was motivated to develop this approach precisely for the reason you indicated in your message, ie., when the kinetic profile is not accurately described by standard compartmental pharmacokinetic models. The catch with my approach is that you need to have enough times points at properly spaced intervals such that the AUC can be accurately estimated by linear and/or log-linear trapezoidal rule calculations. Here is the reference for this approach: Kowalski, K.G. and Karim, A. A Semicompartmental Modeling Approach for Pharmacodynamic Data Assessment. J. Pharmacokin. & Biopharm., 23:307-322 (1995). If you decide to try the semicompartmental modeling approach, let me know if I can be of further assistance. Ken Kowalski G.D. Searle Skokie, IL