Data Construct / ADVAN selection

From: "Sam T" <samt4@hotmail.com> Subject: Data Construct / ADVAN selection Date: Tue, 03 Apr 2001 13:11:17 -0000 Dear NONMEM users, I would like to use NONMEM to do some population modeling and I have a couple of questions. First, is the data item specified correctly for the following single-dose infusion type data (Inf. time=2)? Second what kind of structural model would be appropriate for these data, and is it reasonable to assume that the ADVAN1 or 3 /Trans1 or 4 could give an adequate model for such data? For about 75 subjects, we have a single-dose infusion (Time of infusion, IDUR=2 hrs.) applied daily. I treat these data as a zero order infusion with idur=2, and I used the folowing data item for one subject: DV is concentration in ng/mL, time is in hour, and AMT(dose) is in mg. I tried 2 little control streams as follow: Sub. Dosemg Time-hrs. DV-ng/ml RATE IDUR MDV EVID 1 150 0 0 -1 2 1 0 1 . 0 0 . . 0 0 1 . 0.1 . . . 1 0 1 . 1 1.328 . . 0 0 1 . 2 1.68 . . 0 0 1 . 2.083 1.28 . . 0 0 1 . 2.167 1.2 . . 0 0 1 . 2.33 1.024 . . 0 0 1 . 2.5 0.936 . . 0 0 1 . 3 0.752 . . 0 0 1 . 4 0.472 . . 0 0 1 . 5 0.38 . . 0 0 1 . 8 0.18 . . 0 0 1 . 14 0.12 . . 0 0 2 340 0 0 -1 2 1 1 2 . 0 0 . . 0 0 2 . 0.1 . . . 1 0 2 . 1 3.34 . . 0 0 2 . 2 3.52 . . 0 0 2 . 2.083 2.9 . . 0 0 2 . 2.167 2.58 . . 0 0 2 . 2.33 2.06 . . 0 0 2 . 2.5 1.86 . . 0 0 2 . 3 1.4 . . 0 0 2 . 4 0.45 . . 0 0 2 . 5 0.53 . . 0 0 2 . 8 0.315 . . 0 0 2 . 14 0.167 . . 0 0 One Comp.: $PROB Population PK 1 comp. $INPUT ID AMT TIME DV RATE IDUR MDV EVID $DATA Data_Inf $SUBS ADVAN1 TRANS2 $PK V=THETA(1)+ETA(1) CL=THETA(2)+ETA(2) S1=V/1000 ;where Dose is in mg and DV is in ng/ml IF(AMT.GT.0) NRT=AMT/IDUR ;NRT is nominal rate of infusion R1=NRT $ERROR Y=F+ERR(1) $THETA (0.0001,150,10000) (0.0001,50,10000) $OMEGA 0.25 0.25 $SIGMA 0.04 $EST NOABORT SIGDIGITS=4 MAXEVAL=900 POSTHOC PRINT=5 $COV $TABLE ... Two Comp.: $PROB Population PK 2 comp. $INPUT ID AMT TIME DV RATE IDUR MDV EVID $DATA Data_Inf $SUBS ADVAN3 TRANS4 $PK CL=THETA(1)+ETA(1) V1=THETA(2)+ETA(2) Q=THETA(3)+ETA(3) V2=THETA(4)+ETA(4) S1=V1/1000 ; where Dose is in mg and DV is in ng/ml. IF(AMT.GT.0) NRT=AMT/IDUR ; NRT is the nominal rate of infusion. R1=NRT $ERROR Y=F+ERR(1) $THETA (0.00001,25,100000) (0.00001,30,100000) (0.00001,30,100000) (0.00001,100,100000) $OMEGA 0.04 0.04 0.04 0.04 $SIGMA 0.2 $EST NOABORT SIGDIGITS=4 MAXEVAL=900 POSTHOC PRINT=5 $COV $TABLE ... I tried some of the basic models but I am not getting expected estimations as I obtained by STS (standard two stage) or the program is terminated by round-off error, so I question whether the way the data step specified is correct or some changes have to be made on control stream(s). If someone has any advice, comments, on the above specification, or suggestions for how to model such data, I would really appreciate it. Thanks in advance. Sam T.