Re: using CLS with Differential Equations

From n.holford@auckland.ac.nz Wed Sep 25 16:18:40 1996 Subject: Re: using CLS with Differential Equations > As an example, suppose one wants to do PK/PD modeling given both PK and > PD data, using CLS for PK and an effect compartment for PD. If so, in > the first step, from PK data and CLS, one would obtain the individual > concentration predictions calculated at each effect observation time, > and save them under a new data item, say, CP. Then, in the second step, > from PD data and an effect compartment, one would use the NONMEM control > stream, whose fragment looks like the following, where DV denotes > the effect observation. > > > $INPUT ID TIME DV ... CP > $PK > KEO=THETA(1) > INPUT=CP > $DES > DADT(1)=KEO*(INPUT-A(1)) > > > Hope this helps. I am afraid not. The code above will not work properly because it assumes a fixed value for CP during the integration step One way to deal with this is to save individual estimates (posthoc) of the THETAs used by CLS in the output of the CLS run. Then read these values in as data. The values are then passed to CLS so that CLS can predict A(1) in the DES block. That way the DE solver can know A(1) at each time point that the DES subroutine is called. This can be at any time in the interval between two effect observation times. The question I have for you is can CLS be used in this way? Will PREDPP work if you embed the verbatim code that calls CLS in the DES block? -- 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