PK/PD problem using ADVAN6 [GM000245]

From:"Bachman, William" Subject:[NMusers] PK/PD problem using ADVAN6 [GM000245] Date:Fri, March 1, 2002 4:58 pm Tarun, I got a reasonable fit to your data for one individual with minor modifications to your control stream and data file. the data file: The dose to cmt 3 constitutes setting the initial condition in cmt 3. As such, instead of "1" it should be a number reflecting the steady state effect in the absence of drug, KIN/KOUT. You may use the observed effect at time zero if that's all you have (or an average baseline value prior to dosing). I used the observed effect at time zero here for the "dose" to cmt 3. Alternatively, model KIN as a steady state infusion, R3 (see Manual VIII, Exogenous Supplementation Example, p. 312). (I also modified the data (added a leading comma) to be compatible with PDx-Pop (and still fully NONMEM compatible)). C,Data Desc: tarun,,,,, C,ID,VOL,TIME,DV,AMT,CMT ,1,91.825,0,.,3000000,1 ,1,91.825,0,.,43916,3 ,1,91.825,0,43916,.,3 ,1,91.825,168,.,3000000,1 ,1,91.825,168,16638,.,3 ,1,91.825,336,.,3000000,1 ,1,91.825,336,3349,.,3 ,1,91.825,504,.,3000000,1 ,1,91.825,504,6183,.,3 ,1,91.825,672,.,3000000,1 ,1,91.825,672,5707,.,3 the control stream: You do need to use ERR(1) for an individual. I assume that you will input each individuals PK parameters via the data file when you move to the population model (unless there is VERY LITTLE PK variability). The "F3" statement was not needed. (There is a value in starting with an individual model, it starts off simple and you can simulate the individual to see if your initial estimates are in the ballpark. In fact, I would simulate full profiles to assure you are getting the "shape" you anticipate, your data are all trough measurements.) $PROB POP PK/PD Model $DES $INPUT C ID VOL TIME DV AMT CMT $DATA mydata.csv IGNORE=C $SUBROUTINE ADVAN8 TRANS=1 TOL=3 $MODEL NCOMP=3 COMP=(GUT) COMP=(CENTRAL) COMP=(EFFECT) $PK KA=0.042 KE=0.022 V2=VOL S2=V2 IC50=THETA(1);*EXP(ETA(1)) KOUT=THETA(2);*EXP(ETA(3)) KIN =THETA(3);*EXP(ETA(2)) ;F3=KIN/KOUT $DES DADT(1)=-KA*A(1) DADT(2)=KA*A(1)-KE*A(2) CE=A(2)/V2 DRUG1=1-CE/(CE+IC50) DADT(3)=KIN*DRUG1-KOUT*A(3) $THETA (0, 497) ;IC50 (0, 0.008) ;KOUT (0, 353) ;KIN $OMEGA 0.4 $ERROR Y=F+ERR(1) IPRED=F $EST MAXEVAL=1000 PRINT=5 $TABLE ID TIME CMT FILE=T2.TAB