RE: problem with simulation

From: "Nick Holford" Subject: RE: [NMusers] problem with simulation Date: Tue, November 30, 2004 2:27 pm Kai Wu, I am not really sure what differences you find between NONMEM and Scientist simulations but it looks like the initial conditions are incorrect. This could explain why the AUCs in this CMT are low. In the fragment of data you give there is no AMT for CMT 4 and 5 at time zero so it seems you are assuming that the initial state of these compartments is zero. That is unlikely for a physiological turnover model. So I suggest you add two records for each subject at time zero. An AMT of 1 is put in each compartment to initialize it e.g. #ID TIME AMT DV CMT EVID OCC 1 0 1 . 4 1 1 ; initialize CMT 4 1 0 1 . 5 1 1 ; initialize CMT 5 1 0 0 . 4 0 1 ; Observation for CMT 4 1 0 0 . 5 0 1 ; Observation for CMT 5 Then in $PK you should use the bioavailability fraction trick to get the correct initial value in these compartments. You don't give the DADT for the second PD compartment 5 so I am guessing it is a simple turnover model. F4 = KIN/KOUT ; Compartment 4 initial value F5 = KIN5/KOUT5 ; Compartment 5 initial value The amount in these compartments at time zero is then calculated from the AMT (with a nominal value of 1) at time 0 times the bioavailability fraction (the desired initial value). When using this model for simulation the run times are probably not very long but if you use if for estimation you may be able to shorten run times by writing more efficient code. All the code in $DES is computed many times in order to solve the differential equations. It is therefore a good idea to keep all unnecessary calculations out of this block e.g. I would write this in $PK and remove these constant assignments out of $DES. IF (NEWIND.LE.1) THEN ; this is only executed once per subject KTC=30000000 KALB=5000 QTC=0.0000007 QALB=0.00055 MW=362.47*(10**6) ENDIF You could also compute DCP=CP*0.12 just once in $DES and use this value instead of multiplying CP*0.12 in several different places in the $DES code. Nick -- Nick Holford, Dept Pharmacology & Clinical Pharmacology University of Auckland, 85 Park Rd, Private Bag 92019, Auckland, New Zealand email:n.holford@auckland.ac.nz tel:+64(9)373-7599x86730 fax:373-7556 http://www.health.auckland.ac.nz/pharmacology/staff/nholford/