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Re: Effect-compartment model

From: Ayyappa Chaturvedula <ayyappach>
Date: Tue, 3 Dec 2019 07:11:49 -0600

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-singla
te:
>
> 
> Hi Everyone,
>
> I am trying to relate my compound, THC and metabolite, THC-OH, concentrati=
ons to psychological highness (on scale of 0-10) using effect compartment ap=
proach. This effect compartment model is well validated in literature for th=
ese two compounds. When I run my model, I get the following error. I have tr=
ied ADVAN 6,8 AND 13 but no success so far. I have attached sample of my dat=
aset 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 e=
quates to highness. CMT 1 and CMT4 denote THC and THCOH concentration in cen=
tral 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 cle=
arance for THC
> V1 =THETA(2)*EXP(ETA(2)) ; V - THC - Central Co=
mp
> 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 cl=
earance for THC-OH
> V4 =THETA(6)*EXP(ETA(6)) ; V - THCOH - Central C=
omp
> V5 =THETA(7)*EXP(ETA(7)) ; V - THCOH - Peripher=
al Comp
> CL =THETA(8)*EXP(ETA(8)) ; Clearance
> KE01 =THETA(9)*EXP(ETA(9)) ; rate constant for THC e=
ffect 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**HIL=
L))))
> 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-singla
> 518.577.5881
>

Received on Tue Dec 03 2019 - 08:11:49 EST

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