$DES and T

From: "LSEN (Lars Erichsen)" lsen@novonordisk.com Subject: [NMusers] $DES and T Date: Wed, February 9, 2005 7:29 am Dear Nonmem users, I have a question concerning the use of $DES and the continous time variable T: I want to compute a concentration at any time point T and use it as input to a PD model (see code below). I get the warning (48): DES defined items are computed only when event time increases... Does this mean that CONC is only recomputed at observed time points (I do not have any dosing events)? What happens between these time points? When I print out to a table the first CONC value is 0 - even if TIME>0. Results change if I add new data records to the data set with MDV=1 and new TIME points. Thanks in advance, Lars. $SUBROUTINES ADVAN6 TOL 5 $MODEL COMP=(EFFECT) $PK TVKIN=THETA(1) KIN=EXP(TVKIN) TVKOUT=EXP(THETA(2)) KOUT=TVKOUT*EXP(ETA(1)) TVTH=THETA(3) TH=EXP(TVTH) K=6.41 V=0.127 KA=1.35 $ERROR IPRE=A(1) Y=1+IPRE+ERR(1); $DES CONC=DOSE*KA/(K-KA)/V*(EXP(-KA*T)-EXP(-K*T)) KIN1=0 IF(CONC.GT.TH) KIN1=1 DADT(1)=KIN*KIN1-KOUT*A(1)

From: "Sam Liao" sliao@pharmaxresearch.com Subject: Re: [NMusers] $DES block and T Date: Wed, February 9, 2005 6:38 pm Hi Lars: You do need to have the MDV record with time equal to zero in order to solve the differential equation correctly. You've done the right thing paying attention to the warning msg from nmv. It is trying to tell you that the ODE solver start from a time point which is not zero. That is why the results are different. Also on a different issue about your PKPD model, instead of using a threshold concentration in your model, have you try a Emax model (Hill's equation) with large gamma coefficient which can also give you a steep function to mimic the threshold model you have. Best regards, Sam Liao _______________________________________________________