Re: kinetic interpolation and effect compartments

From n.holford@auckland.ac.nz Tue Sep 24 14:39:53 1996 Subject: Re: kinetic interpolation and effect compartments I am bit puzzled by this reply. What do you mean by a "kinetic profile"? If you mean predicted concs at the times of each of effect observation this is not much help in using a parametric model for an effect compartment although it might be used for one of the semi-paramtric loop collapsing methods for estimating the equilibration half-time. I presume you do not mean a set of PK parameters such as CL, V, KA, because CLS does not deal with this kind of parameterisation. Or perhaps you mean that there are a set of parameters from CLS that can be used? If this is the case then an example control stream would be helpful. If one can use CLS to interpolate the predicted PK concs then it should be possible to use these with a differential equation defined model to predict effect cpt concs or use a physiological delay model (aka indirect response model). I have used a cubic splines with MKMODEL to interpolate individual PK data and then used a DE model to estimate effect cpt model parameters. It would be nice to see how to do this using CLS in the NONMEM environment. -- Nick Holford, Dept Pharmacology & Clinical Pharmacology University of Auckland, Private Bag 92019, Auckland, New Zealand email:n.holford@auckland.ac.nz tel:+64(9)373-7599x6730 fax:373-7556 http://www.phm.auckland.ac.nz/Staff/NHolford/nholford.html