RE: Indirect response model in NONMEM

From:"Luann Phillips" luann.phillips@cognigencorp.com Subject: RE: [NMusers] Indirect response model in NONMEM Date: Wed, August 25, 2004 6:10 pm Toufigh, Question: Can you actually measure cmt=5? If yes: Add a record to your dataset at time=0 (very first record) with cmt=5, amt=first concentration value from cmt=5, and dv=missing. In the control stream add F5=1*exp(eta(n)) to allow for estimation of measurement error in the first concentration of cmt=5. You can keep the first concentration from cmt=5 as an observation record in addition to using it as a dose record but I usually delete it. If no: Add a record to your dataset at time=0 (very first record) with cmt=5, set amt=1. All later predictions of A(5) will be relative concentrations (ie., fractional changes) If you can not measure A(5), you will never be able to estimate a baseline value for the compartment. You assume a beginning concentration (amt=1) and then your model estimates the relative impact that the drug has on CMT=5. Note: In both cases, you should treat it as a bolus dose. If whatever A(5) represents is at steady-state prior to introducing the drug, then also use SS=1. (Review the bug about ADVAN9 and the SS6 routine). Also, make sure that IEFF is restricted between 0 and 1 to prevent your input rate for cmt=5 from becoming negative. Regards, Luann