Is your model a good fit to the data (e.g. as judged by diagnostic plots)? If so, I would guess that your units may be the problem and you may need to include a scaling factor for V in S2. eg. S2= V/1000. So check that your units are compatible for dose, V and your DV. I assume that your fixed value for Ka is ok (you have a good basis for the value you are using). If your model is not a good fit to your data, you may need better initial estimates. It's not usually a good idea to impose un-natural limits on parameters, like a fixed upper bound for PK parameters. (but setting a lower bound on pk parameters does make sense.) It's also generally a good idea to give a subject for your posts so others can judge whether they want to contribute (or not) and there also will be a thread to follow. Sent: Saturday, March 5, 2011 12:02:54 PM Hi I am trying to build a structural model for an oral drug. I am getting extremely large and unreasonable values for vd, eg a billion L, putting an upper limit on theta will give a near boundary warning. Does anyone have an idea why this might occur and how to solve it. This is part of the input file: $SUBROUTINE ADVAN2 TRANS2 $PK TVCL = THETA(1) CL = TVCL*EXP(ETA(1)) V = THETA(2) KA = THETA(3) S2 = V $THETA (0,10) $THETA (0,20) $THETA 2 FIXED Best regards Susan
