$PROBLEM 1 $INPUT ID ;ID TIME ;TIME AMT ;Amount LDV=DV ;Concentration (log scale) CMT ;Compartment MDV ;Missing data EVID ;Evidence ID WT ;Body weight $DATA Simulated_run1.csv IGNORE=# IGNORE(DV.EQ.0) $SUBROUTINE ADVAN5 TRANS1 $PRIOR NWPRI ;Number of parameters in prior approach NTHETA=12 NETA=11 NTHP=7 NEPS=1 NETP=4 NPEXP=1 $MODEL COMP=(1) ;(ABSORB,DEFDOSE) COMP=(2) ;(CENTRAL) COMP=(3) ;(PERIPHERAL 1) COMP=(4) ;(PERIPHERAL 2) COMP=(5) ;(TRANSIT 1) COMP=(6) ;(TRANSIT 2) $PK TVCL = THETA(1)*((WT/18)**0.75); ;Typical value of CL CL = TVCL*EXP(ETA (1)); ;Individual value of CL TVV2 = THETA(2)*((WT/18)**1); ;Typical value of V2 V2 = TVV2 *EXP(ETA (6)); ;Individual value of V2 TVQ3 = THETA(3)*((WT/18)**0.75); ;Typical value of Q3 Q3 = TVQ3*EXP(ETA (7)); ;Individual value of Q3 TVV3 = THETA(4)*((WT/18)**1); ;Typical value of V3 V3 = TVV3*EXP(ETA (8)); ;Individual value of V3 TVQ4 = THETA(5)*((WT/18)**0.75); ;Typical value of Q4 Q4 = TVQ4*EXP(ETA (2)); ;Individual value of Q4 TVV4 = THETA(6)*((WT/18)**1); ;Typical value of V4 V4 = TVV4*EXP(ETA (9)); ;Individual value of V4 TVMT = THETA(7); ;Typical value of MT MT = TVMT*EXP(ETA(3)); ;Individual value of MT RELF = THETA(12); ;Scaling of F due to different population compared to prior model TVF1 = THETA(9); ;Typical value of F F1 = TVF1*RELF*EXP(ETA(4)); ;Individual value of F TVCV = THETA(10); ;Typical conversion factor: cenous-capillary CV = TVCV*EXP(ETA(10)); ;Individual conversion factor: cenous-capillary NN = 2 ; Number of transit compartments KTR = (NN+1)/MT ;Calculation of KTR K15 = KTR K56 = KTR K62 = KTR K20 = CL/V2 K23 = Q3/V2 K32 = Q3/V3 K24 = Q4/V2 K42 = Q4/V4 S2 = V2/1000 ;Scaling of volume $ERROR CP = A(2)/S2; ;Capillary concentrations VP = CP*CV; ;Venous concentrations IPRED = 0 IF(CMT.EQ.2.AND.A(2).GT.0) IPRED = LOG(CP) IF(CMT.EQ.3.AND.A(2).GT.0) IPRED = LOG(VP) IF(CMT.EQ.2) THEN W = THETA(8)*EXP(ETA (5)) ;Residual error for capillary measurments ELSE W = THETA(11)*EXP(ETA (11)) ;Residual error for venous measurments ENDIF Y = IPRED + W*EPS(1) IRES = DV-IPRED IWRES = IRES/W IF(AMT.GT.0) DTIM = TIME ;Calculation of time after dose TAD = TIME-DTIM $THETA (0,7.654180) ; 1.CL (0,313.7700) ; 2.V2 (0,9.779240) ; 3.Q3 (0,274.2410) ; 4.V3 (0,10.80280) ; 5.Q4 (0,3490.670) ; 6.V4 (0,1.366910) ; 7.MT (0,0.304931) ; 8.W_CP 1 FIX ; 9.F (0,0.379853) ; 10.CV (0,0.666114) ; 11.W_VP (0,0.726486) ; 12.REL_F $THETA 7.5 FIX ; 1. CL Prior $THETA 247 FIX ; 2. V2 Prior $THETA 13.1 FIX ; 3.Q3 Prior $THETA 254 FIX ; 4.V3 Prior $THETA 10.8 FIX ; 5.Q4 Prior $THETA 3340 FIX ; 6.V4 Prior $THETA 2.15 FIX ; 7.MT Prior $THETA 31 FIX ; Degree of freedom of OMEGA block (Uninformative = # of omega) $THETA 27 FIX ; Calculated from 2*(ETA**2/SE_ETA**2) - 1 $THETA 50 FIX $THETA 41 FIX $OMEGA 0.043826 ; 1.CL VAR 0.047757 ; 2.Q4 VAR 0.573941 ; 3.MT VAR 0.113772 ; 4.F VAR 0 FIX ; 5.W_VP VAR 0.664941 ; 6.V VAR 0 FIX ; 7.Q3 VAR 0 FIX ; 8.V3 VAR 0.048554 ; 9.V4 VAR 0 FIX ; 10.CV VAR 0 FIX ; 11.W_VP VAR $OMEGA BLOCK(7) FIX ;For prior 2.91E-02 1.81E+00 7.04E+02 -7.63E-02 -5.44E+01 7.11E+00 5.22E-01 4.57E+01 1.08E+01 2.30E+02 1.38E-02 -8.42E-01 4.68E-01 1.69E+00 1.27E-01 2.33E+00 2.06E+03 -1.68E+02 4.97E+02 4.82E+00 1.42E+04 -1.84E-02 -6.86E+00 6.61E-01 -1.93E-01 4.15E-02 -1.81E+01 1.06E-01 $OMEGA 0.043300 FIX ; 1.CL VAR Prior $OMEGA 0.048700 FIX ; 2.Q4 VAR Prior $OMEGA 0.494000 FIX ; 3.MT VAR Prior $OMEGA 0.073500 FIX ; 4.F VAR Prior $SIGMA 1 FIX $ESTIMATION SIGL=6 NSIG=2 MAXEVAL=0 PRINT=1 POSTHOC METHOD=1 INTER MSFO=msf1 NOABORT $COVARIANCE PRINT=E MATRIX=R $TABLE ID AMT TIME TAD CL V2 V3 V4 Q3 Q4 MT F1 W ETA1 ETA2 ETA3 ETA4 ETA5 ETA6 ETA7 ETA8 ETA9 CP VP IPRED MDV EVID CMT WT IRES IWRES WRES CWRES NPDE NOPRINT ONEHEADER FILE=mytab1