Re: kinetic interpolation and effect compartments

From rs@chdr.leidenuniv.nl Thu Sep 26 23:53:39 1996 Subject: Re: kinetic interpolation and effect compartments Dear Ken, you wrote > 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 > > But after my request for a recursive implementation (which from your paper I gather is necessary) Alison wrote as a response to Ruedi's reply: >Ruedi Port gives this example of a recursive $PRED: > >$PRED > > IF (TIME.EQ.0) Celast = 0 ; or some other initial value > Cenew = ... Celast ... (function of Celast and the PK parameters) > effect = ... (function of Cenew and more parameters > Y = ... effect ... EPS( ) > Celast = Cenew > >This can only work with individual data, i.e., when there are no >inter-individual (population) etas. > >But Rik's code was for population data. > >Maybe someday NM-TRAN will be able to handle a recursive $PRED, >but this is far off (not even with NONMEM V). > >It is necessary to write one's own PRED for the recursive >case with population data. If the functions are relatively simple >and the dosing is simple, this is not so very difficult a task. >Information in the User's Guides (I and VI) would be helpful. > >Alison Boeckmann > Does this mean that the only way to implement it in NONMEM is by using a differential equation in connection with slopes and intercepts for the interpolating straight lines? Or can you write down an explicit solution after all, since you say that it is easily implemented in NONMEM? Kindest regards, Rik Schoemaker, CHDR, Leiden, NL