Two formulation of the same Drug

From: Gautam Baheti Subject: [NMusers] Two formulation of the same Drug Date: Tue, 30 Apr 2002 07:08:55 -0700 (PDT) Hello NONMEM users, I have been using NONMEM to determine the apparent clearance (CL/F) of two different formulations (X and Y) of a drug in a population model. It has been established from previous studies that formulation X has a higher bioavailability hence a lower apparent clearance (30% higher) than formulation Y. Twenty seven patients are on formulation X and 21 patients on formulation Y. I am trying to use formulation type as a covariate and have been unsuccessful to get it to run when I use both the formulations together, but I get the expected value when I break them into two separate data sets. I have tried different estimates for Theta (5) the error I am getting is ? The estimates of theta are near the boundary.? or at times I get Minimization is successful but I am not getting and estimates. My control file is as follows $PROB ANALYSIS2 $INPUT ID TIME AMT DV SS DI=II TAD DOSE $DATA DOSE.PRN IGNORE=C $SUBROUTINES ADVAN2 TRANS2 $PK TVCL=THETA (1)+THETA (5)*DOSE CL=TVCL*EXP (ETA (1)) TVV=THETA (2) V= TVV*EXP (ETA (2)) K= CL/V IF (DOSE.EQ.1) TVKA=THETA (3) KA=TVKA IF (DOSE.EQ.0) TVKA=THETA (4) KA=TVKA S2=V $THETA (0,105,500) (1,1000, 5000) (0.25 FIXED) (1.35 FIXED)(5,20,100) $ERROR Y=F*(1+ERR (1)) $OMEGA (0.3) $SIGMA (0.3) $EST MAXEVAL=1000 PRINT=5 $COV Any help in this regard will be appreciated. Thank you, Gautam Baheti