Hi Xin yi, You may try defining compartment 4 is your observation compartment. **And then in $ERROR module, put IPRED=A(4) or IPRED=F.
Hong Lu On Fri, Feb 11, 2011 at 10:35 AM, xin yi <[email protected]> wrote: > Hi all, > > I'm new to nonmem and would be grateful for some pointers and help. I'm > trying to do a pk-pd sequential modelling. I have modelled the PK data but > I've encountered problems with PD. My PD model is a indirect inhibition > response model. I have tried to change my initial estimates reduce the > number of parameters in the model, but nothing seem to get me a good > convergence. At different times, NONMEM gives me different error messages > such as "parameter estimates near its boundary", "Minimisation successful. > However problems occured with the minimization"(blank entries for omega or > sigma estimates in the results file) *** or the "r matrix is > algorithmically singular and non-positive definite". I have a few questions: > > 1) Are there any errors in the way I input my control and data file? > 2) Under $ERROR in the control file, did I define it correctly with > EFF=A(4), Y**=EFF+EFF*ERR(1)+ERR(2)*? Or should it be IPRED=F, > Y=F+F*ERR(1)+ERR(2). > 3) Why are they no estimates for sigma and omega in the results file? I > have been constantly changing my initial estimates for omega and sigma but > they always give me nil results. > > I appreciate any help on this matter. Thanks! > > Regards, > X.Y. Ng > * > This is an example of my control file: > > $PROB RUN# pd_3_advan6 > $INPUT ID TIME DV AMT CMT ADDL II MDV V2I V3I QI CLI KAI > > $DATA FINAL2.2.CSV IGNORE=C > $SUBROUTINES ADVAN6 TRANS1 TOL=3 > $MODEL > COMP=DEPOT > COMP=CENTRAL > COMP=PERIPH > COMP=EFFECT ;$MODEL defines the no of compartments in the model > > $PK > > V2=V2I > V3=V3I > Q=QI > CL=CLI > KA=KAI > S2=V2 > S3=V3 > KIN=THETA(1)*EXP(ETA(1)) > KOUT=THETA(2)*EXP(ETA(2)) > IC50=THETA(3)*EXP(ETA(3)) > F4=KIN/KOUT > > $DES > DADT(1)=-KA*A(1) > DADT(2)=KA*A(1)-Q/V2*A(2)+Q/V3*A(3)-CL/V2*A(2) > DADT(3)=-Q/V3*A(3)+Q/V2*A(2) > INH =A(2)/(IC50+A(2)) > DADT(4)=KIN*(1-INH)-KOUT*A(4) > > $ERROR > CP2=A(2)/S2 > CP3=A(3)/S3 > ;IPRED=F > EFF=A(4) > Y=EFF+EFF*ERR(1)+ERR(2) > > $THETA (0,0.281) ;POPKin > $THETA (0,0.003) ;POPkout > $THETA (0,2) ;POPIC50 > > $OMEGA 0.003 ;BSV Kin > $OMEGA 0.003 ;BSV Kout > $OMEGA 0.003 ;BSV IC50 > > $SIGMA 0.01 ;ERRCCV > $SIGMA 0.0015 ;ERRADD > > $ESTIMATION METHOD=1 INTERACTION NOABORT MAXEVAL=9990 PRINT=10 POSTHOC > $COVARIANCE > $TABLE ID TIME DV AMT CMT NOPRINT ONEHEADER FILE=pd_3_advan6.TAB > > and an example of my data: > > * CID TIME DV AMT CMT ADDL II MDV V2I V3I QI CLI KAI 101 0 0 100 1 2 8 1 > 44.55 11.78 1.07 3.37 0.62 101 0 0 1 4 0 0 1 44.55 11.78 1.07 3.37 0.62 > 101 3 243 0 4 0 0 0 44.55 11.78 1.07 3.37 0.62 101 7 293 0 4 0 0 0 44.55 > 11.78 1.07 3.37 0.62 101 11 261 0 4 0 0 0 44.55 11.78 1.07 3.37 0.62 101 > 15 260 0 4 0 0 0 44.55 11.78 1.07 3.37 0.62 101 19 277 0 4 0 0 0 44.55 > 11.78 1.07 3.37 0.62 101 23 290 0 4 0 0 0 44.55 11.78 1.07 3.37 0.62 101 > 35 233 0 4 0 0 0 44.55 11.78 1.07 3.37 0.62 101 39 271 0 4 0 0 0 44.55 > 11.78 1.07 3.37 0.62 101 43 274 0 4 0 0 0 44.55 11.78 1.07 3.37 0.62 101 > 47 276 0 4 0 0 0 44.55 11.78 1.07 3.37 0.62 * > *
