RE: Fx

From: Ekaterina Gibiansky GibianskyE@guilfordpharm.com Subject: RE: [NMusers] Fx Date:Tue, May 25, 2004 9:28 am Paul, F2 is a fraction of dose amount in your data file that is transfered in compartment 2. That's it, NONMEM does not know anything else about it. By default it is 1. So you do not need to mention F2 in the code (and yes, volume and clearance are then apparent values CL/F, V/F) unless you want to estimate F or fix it to some specific value. However, with oral dosing and linear model you cannot estimate F, it is not identifiable. So, no need for F2 in the model you have now. If you were to have a nonlinear model (say, relative F2 is dose dependent), where you need THETA(s) for F2, CL and V would not be apprarent values, and you should not divide them by F2. S2 is a scaling parameter that NONMEM uses to convert PREDICTED amount in the compartment into predicted concentration to then compare it with the observed value. That predicted amount is computed using the dose that entered the compartment, i.e. with F2 already figured in. You should not include it in the scaling again. In the differential equation block, V2 and S2 are equivalent (as Bill says) only in the sense that NONMEM will not complain and will spit the estimates just fine (if the model is linear). But the estimate of CL will be in different (inconsistent) units than V, if V/1000 is used for estimation. For a nonlinear model (depending on how it is written) using S2 may lead to problems/errors. Katya *-------------------- Ekaterina Gibiansky, PhD Head, Pharmacometrics & Principal Scientist Guilford Pharmaceuticals Inc Phone: (410)-631-6828 Fax: (410)-631-6828 E-mail: gibianskye@guilfordpharm.com