Hi Sumeet, Please check if your control stream accurately mentioned the column names. I don’t see AMT as third column in $INPUT where your dose is listed.
Regards, Ayyappa > On Dec 2, 2019, at 9:55 PM, Singla, Sumeet K <sumeet-sin...@uiowa.edu> wrote: > > > Hi Everyone, > > I am trying to relate my compound, THC and metabolite, THC-OH, concentrations > to psychological highness (on scale of 0-10) using effect compartment > approach. This effect compartment model is well validated in literature for > these two compounds. When I run my model, I get the following error. I have > tried ADVAN 6,8 AND 13 but no success so far. I have attached sample of my > dataset and the control stream. Both THC and THC-OH has peripheral > compartments. TYPE 3 equates to THC conc, TYPE2 equates to metabolite conc, > and TYPE 1 equates to highness. CMT 1 and CMT4 denote THC and THCOH > concentration in central compartment, respectively. > > Please let me know of any possible solutions. > > “OCCURS DURING SEARCH FOR ETA AT A NONZERO VALUE OF ETA > NUMERICAL DIFFICULTIES WITH INTEGRATION ROUTINE. > > NO. OF REQUIRED SIGNIFICANT DIGITS IN SOLUTION VECTOR > > TO DIFFERENTIAL EQUATIONS, 3, MAY BE TOO LARGE. “ > > ID TIME > DV CMT TYPE1 TYPE2 TYPE3 > MDV > 1204 > 9:38 > 21138 > 79.9 > 1 > 0 > 0 > 1 > 1 > 1204 > 9:38 > . > 7 > . > 1 > 0 > 0 > 0 > 1204 > 9:38 > . > 10.1 > 4 > 0 > 1 > 0 > 0 > > > $SUBROUTINE ADVAN6 TRANS1 TOL=3 > > $MODEL NCOMP = 6 > COMP = (CENTRAL) > COMP = (PERIPH) > COMP = (EFFTHC) > COMP = (METABOL) > COMP = (METABOL2) > COMP= (EFFTHCOH) > > $PK > Q1 =THETA(1)*EXP(ETA(1)) ; Inter-compartment > clearance for THC > V1 =THETA(2)*EXP(ETA(2)) ; V - THC - Central Comp > V2 =THETA(3)*EXP(ETA(3)) ; V - THC - Peripheral Comp > K14 =THETA(4)*EXP(ETA(4)) ; Metabolite conversion > Q2 =THETA(5)*EXP(ETA(5)) ; Inter-compartment > clearance for THC-OH > V4 =THETA(6)*EXP(ETA(6)) ; V - THCOH - Central Comp > V5 =THETA(7)*EXP(ETA(7)) ; V - THCOH - Peripheral > Comp > CL =THETA(8)*EXP(ETA(8)) ; Clearance > KE01 =THETA(9)*EXP(ETA(9)) ; rate constant for THC > effect compartment > KE02 =THETA(10)*EXP(ETA(10)) ; rate constant for THCOH > effect compartment > S1=V1 > S4=V4 > A_0(1)=0 > A_0(3)=0 > A_0(4)=0 > A_0(6)=0 > > $DES > C1=A(1)/V1 > C3=A(3) > C4=A(4)/V4 > C6=A(6) > DADT(1) = (Q1/V2)*A(2) - (Q1/V1)*A(1) - K14*A(1) > DADT(2) = (Q1/V1)*A(1) - (Q1/V2)*A(2) > DADT(3) = KE01*C1 - KE01*A(3) > DADT(4) = K14*A(1) - (CL/V4)*A(4) - (Q2/V4)*A(4) + (Q2/V5)*A(5) > DADT(5) = (Q2/V4)*A(4) - (Q2/V5)*A(5) > DADT(6) = KE02*C4 - KE02*A(6) > > $ERROR > CE1=A(3) > CP=A(1)/V1 > CE2=A(6) > CM=A(4)/V4 > EMAX = THETA(11)*EXP(ETA(11)) > EC50 = THETA(12)*EXP(ETA(12)) > HILL = THETA(13)*EXP(ETA(13)) > CONC = CP*(1 + ERR(1)) + ERR(2) > CONCMET = CM + ERR(3) > E = EMAX*(((CE1**HILL)+(CE2**HILL))/((EC50**HILL)+((CE1**HILL)+(CE2**HILL)))) > EFF = E + ERR(4) > IF(TYPE3.EQ.1) IPRED = CP > IF(TYPE2.EQ.1) IPRED = CM > IF(TYPE1.EQ.1) IPRED = E > Y = (CONC*TYPE3) + (EFF*TYPE1) + (CONCMET*TYPE2) > > $THETA > (0, 6.964) ;[Q1] > (0, 20) ;[V1] > (0, 50) ;[V2] > (0, 10) ;[K14] > (0, 10) ;[Q2] > (0, 40) ;[V4] > (0, 50) ;[V5] > (0, 102.95) ;[CL] > (0,5,50) ;[KE01] > (0,5,50) ;[KE02] > 10 FIX ;[EMAX] > (1, 50, 400) ;[EC50] > (0.1, 1,5) ;[HILL] > > $OMEGA > 0.0152 ; [P] omega(1,1) > 0.005 ; [P] omega(2,2) > 0.06 ; [P] omega(3,3) > 0.04 ; [P] omega(4,4) > 0.03 ; [P] omega(5,5) > 0.06 ; [P] omega(6,6) > 0.03 ; [P] omega(7,7) > 0.07 ; [P] omega(8,8) > 0.06 ; [P] omega(9,9) > 0.05 ; [P] omega(10,10) > 0.05 ; [P] omega(11,11) > 0.06 ; [P] omega(12,12) > 0.06 ; [P] omega(13,13) > > $SIGMA > 0.5 ; [ERR1] > 0.5 ; [ERR3] > 0.5 ; [ERR4] > > $SIGMA > 0.00001 FIX ;[ERR2] > > > $EST METHOD=1 MAXEVAL=9999 PRINT=5 SIG=3 NOABORT MSFO=2010-2013.MSF > $COV > > Regards, > > Sumeet K. Singla > Ph.D. Candidate > Division of Pharmaceutics and Translational Therapeutics > College of Pharmacy | University of Iowa > Iowa City, Iowa > sumeet-sin...@uiowa.edu > 518.577.5881 >
