Model Identifiability

Dear NMusers I have collected from several studies PK data from healthy subjects, via IV and SubCut and patients via both routes and would like to model them all together. For all subjects, only one dose level via one administration was given. From exploration of raw data, it is observed that there might be some difference in bioavailability from SubCut between healthy subjects and patients. I tried the model using ADVAN5, the parameterisation is listed below. My questions are: Is the model with six THETAs and ETAs an identifiable model? NOTE: NONMEM run with this model is successful, also the estimates for CL,V2,Q and V3 are similar to results with IV data alone. What is a better way to explore the potential difference in PK between healthy subjects and patients with SubCut? Finally, I also tried to model K12 as K12=0, IF(ROUT.GT.1) K12=EXP(THETA(5)+ETA(5)), could anyone help explain why this is wrong? NONMEM gave the following error message: 0PRED EXIT CODE = 1 0INDIVIDUAL NO. 1 ID=0.10080000E+04 (WITHIN-INDIVIDUAL) DATA REC NO. 2 THETA= 1.10E+00 1.40E+00 5.00E-01 2.50E+00 -1.10E+00 5.00E-01 NUMERICAL DIFFICULTIES OBTAINING THE SOLUTION. THE COEFFICIENT MATRIX IS ALGORITHMICALLY SINGULAR. Thanks for the help. Shuying Yang Clinical Pharmacology Modelling and Simulation GlaxoSmithKline CMT = 1 for SubCut dose record, and CMT=2 for IV dose record ROUT=1 for IV and ROUT=2 for SubCut CL = EXP(THETA(1)+ETA(1)) V2 = EXP(THETA(2)+ETA(2)) Q = EXP(THETA(3)+ETA(3)) V3 = EXP(THETA(4)+ETA(4)) K20 = CL/V2 K23 = Q/V2 K32 = Q/V3 K12 = EXP(THETA(5)+ETA(5)) RO = EXP(THETA(6)+ETA(6)) F1=0 IF(ROUT.GT.1) F1=RO/(1+RO) $THETA 1.0 ; CL 1.2 ; V2 0.5 ; Q 1.5 ; V3 -1.3 ; LOG(KA) /DAY 1.3 ; LOGIT(F1) $OMEGA 0.05 ;CL $OMEGA 0.06 ;V2 $OMEGA 0.1 ; Q $OMEGA 0.05 ;V3 $OMEGA 0.05 ; LOG KA $OMEGA 0.05 ; LOGIT F1 $SIGMA 0.02; PROPORTIONAL 2000; ADDITIVE ----------------------------------------------------------- This e-mail was sent by GlaxoSmithKline Services Unlimited (registered in England and Wales No. 1047315), which is a member of the GlaxoSmithKline group of companies. The registered address of GlaxoSmithKline Services Unlimited is 980 Great West Road, Brentford, Middlesex TW8 9GS.