what is your rationale to use rat data for population analysis with 6 etas?
On Mon, Apr 30, 2012 at 8:41 AM, siwei Dai <[email protected]> wrote: > Hi, NM users: > > I am a new NONMEM user and wish to get help from NM experts. > > I have a data from rats with concentration measured in both plasma and > cerebrospinal fluid . Compared to plasma concentration, the concentration > in brain is relatively small (up to 30 times difference). Due to the big > range of my data, I log-transformed my data. Below is the code I used. I > was able to get NM to run, but obvious bias existed in goodness-of-fit > plot. I worried that there are mistakes in my code. Could anyone take a > look of my code especially the $ERROR code to see what is wrong? > Also, I saw in an earlier discussion on how to get additive error with > log-transformed data, but that was for simple models. Can anybody give some > insights on how to do it with more complex data such as the data I have? > Thank you in advance for your time. > > Siwei > > $SUBROUTINES ADVAN6 TOL=3 > $MODEL > NCOMP=3 > COMP=(COMP1) ;Central compartment > COMP=(COMP2) ;Peripheral compartment > COMP=(COMP3) ;Brain compartment > $PK > TVCL=THETA(1) > CL=TVCL*EXP(ETA(1)) > TVV1=THETA(2) > V1=TVV1*EXP(ETA(2)) > TVQ1=THETA(3) > Q1=TVQ1*EXP(ETA(3)) > TVV2=THETA(4) > V2=TVV2*EXP(ETA(4)) > TVKEQ=THETA(5) > KEQ=TVKEQ*EXP(ETA(5)) ; Equilibration rate constant trough BBB > TVPC=THETA(6) > PC=TVPC*EXP(ETA(6)) ; Partition coefficient at BBB > > K10=CL/V1 > K12=Q1/V1 > K21=Q1/V2 > > S1=MV1 > > $DES > DADT(1)=-K10*A(1)-K12*A(1)+K21*A(2)-KEQ*(A(1)*PC-A(3)) > DADT(2)=K12*A(1)-K21*A(2) > DADT(3)=KEQ*(A(1)*PC-A(3)) > > $ERROR > > IF(AMT.NE.0) THEN > IPRE=LOG(1) > ELSE > IPRE=LOG(F) > ENDIF > > CM=0 > IF (CMT.LE.2) CM=1 > CF=0 > IF (CMT.GE.3) CF=1 > YM = IPRE+ERR(1) ; Plasma > YF = IPRE+ERR(2) ; Brain > > Y=CM*YM+CF*YF > > $EST METHOD=1 PRINT=1 MAX=9999 SIG=3 > $THETA > $OMEGA > $SIGMA > > Here is how the data look like: > ID TIME AMT DV_log MDV CMT > 1 0 180 0 . 1 1 > 1 5 0 0 0.825 0 1 > 1 5 0 0 -0.127 0 3 > 1 15 0 0 0.954 0 1 > 1 15 0 0 -0.011 0 3 > 1 25 0 0 0.937 0 1 > 1 25 0 0 0.137 0 3 > 1 60 0 0 1.015 0 1 > 1 60 0 0 0.188 0 3 > 1 100 0 0 0.567 0 1 > 1 100 0 0 -0.311 0 3 > 1 150 0 0 0.378 0 1 > 1 150 0 0 -0.493 0 3 > 1 180 0 0 -0.159 0 1 > 1 180 0 0 -0.74 0 3 > -- Indrajeet Singh,PhD Sr. Clinical Pharmacokineticist Abbott Labs, North Chicago, IL
