Re: [NMusers] ERROR NUMBER OF BASIC PK PARAMETERS EXCEEDS VALUE OF NPARAM IN $MODEL

From: Alison Boeckmann <alisonboeckmann_at_fastmail.fm>
Date: Wed, 31 Jul 2019 11:03:43 -0700

(1) I agree with Leonid: don't code NPARAM.
NPARAM is required when the user writes a Fortran DES routine, e.g.,
$SUBR DES=mydes
When $DES abbreviated code is present, NMTRAN will count the
basic PK parameters and set NPARAM in the generated MODEL routine.
For example, if you omit NPARAM from the $MODEL record,
the generated MODEL routine sets
      NPAR=007
This is reported in the PREDPP portion of the NONMEM output:
MAXIMUM NO. OF BASIC PK PARAMETERS: 7

If both $DES and NPARAM are present, NPARAM must be at least
as large as the number counted by NMTRAN, but may not be smaller.
(NMTRAN uses the larger value in the MODEL routine.)

(2) You ask:
"It appears that NONMEM wants additional parameters added to NPARAM
when I added calculated value CC in the $DES block. "

The code in $PK is
MIC=0.12 ; SEEKING TIME AND AUC ABOVE 0.12 MCG/ML
The code in $DES is
CC=A(1)/V1
IF(CC.GT.MIC) RT=1

It is MIC that looks to NMTRAN like a basic PK parameter.
You can see the following code in subroutine PK in FSUBS:
     P000002=MIC
     GG(0002,1,1)=P000002

(3) You ask:
"What is also odd to me is that the fault is called on the line
defining DADT(2)."

I'll pass on this one. Sometimes NMTRAN may report an error on a
line near where the error is detected, not the exact line. It may
be easy to fix for this example and yet the fix may break some other
control stream.

-- Alison

On Wed, Jul 31, 2019, at 5:56 AM, Paul Hutson wrote:
> Hello, Leonid, and thank you for the correction on the IWRES and the =

> suggestion on the IRES.
> Regarding NPARAM, you are correct, the model runs if the NPARM count i=
s
> removed from the $MODEL statement. It was curious to me that if it =

> was included that it was counting the calculated value CC in the $DES =

> block as a parameter.
> Take care.
> Paul
>
> Paul Hutson, PharmD, BCOP
> Professor
> UWisc School of Pharmacy
> T: 608.263.2496
> F: 608.265.5421
>
> -----Original Message-----
> From: Leonid Gibiansky <lgibiansky_at_quantpharm.com>
> Sent: Tuesday, July 30, 2019 11:53 PM
> To: Paul Hutson <paul.hutson_at_wisc.edu>; 'nmusers'
> <nmusers_at_globomaxnm.com>
> Subject: Re: [NMusers] ERROR NUMBER OF BASIC PK PARAMETERS EXCEEDS
> VALUE OF NPARAM IN $MODEL
>
> Not sure why would we need NPARAM there, is it necessary? I think one =

> can skip it.
>
> On the different topic, expression for IWRES is not correct:
>
> IWRES=IRES/(IPRED * EPS(1) + EPS(2))
>
> This is the version that should be used:
>
> IWRES=IRES/SQRT(IPRED**2 * SIGMA(1,1) + SIGMA(2,2))
>
> Also it is more traditional to define IRES=DV-IPRED (negative residu=
al
> corresponds to over-predictions; observed=predicted + residual error=
).
>
> Regards
> Leonid
>
>
> On 7/29/2019 2:49 PM, Paul Hutson wrote:
> > I've fixed it by increasing NPARAM until it worked (increasing to 7)=
,
> > but can anyone explain why I get this message for a 3 compartment =

> > model with additional compartments to output a time above a
> > concentration threshold (#4) and AUC while above that concentration =
threshold (#5)?
> > It appears that NONMEM wants additional parameters added to NPARAM =

> > when I added calculated value CC in the $DES block.  What is al=
so odd
> > to me is that the fault is called on the line defining DADT(2). Than=
ks
> > in advance. Paul
> >
> > $SUBROUTINES ADVAN6 TOL=3
> >
> > $MODEL NCOMP=5 NPARAM=6
> >
> > COMP=(CENTRAL DEFDOSE DEFOBS)
> >
> > COMP=(TISU1)
> >
> > COMP=(TISU2)
> >
> > COMP=(TTIME)
> >
> > COMP=(AUCC)
> >
> > ;------------------PK BLOCK
> >
> > $PK
> >
> > MIC=0.12 ; SEEKING TIME AND AUC ABOVE 0.12 MCG/ML
> >
> > TVCL = POP_CL
> >
> > TVV1=POP_V1
> >
> > TVQ2=POP_Q2
> >
> > TVV2=POP_V2
> >
> > TVQ3=POP_Q3
> >
> > TVV3=POP_V3
> >
> > CL=TVCL * EXP(ETA(1))
> >
> > V1=TVV1 * EXP(ETA(2))
> >
> > Q2=TVQ2 * EXP(ETA(3))
> >
> > V2=TVV2 * EXP(ETA(4))
> >
> > Q3=TVQ3 * EXP(ETA(5))
> >
> > V3=TVV3 * EXP(ETA(6))
> >
> > K10=CL/V1
> >
> > K12=Q2/V1
> >
> > K21=Q2/V2
> >
> > K13=Q3/V1
> >
> > K31=Q3/V3
> >
> > ;--------------------DES BLOCK
> >
> > $DES
> >
> > CC=A(1)/V1
> >
> > RT=0
> >
> > IF(CC.GT.MIC) RT=1
> >
> > DADT(1) = - A(1) * (K10 + K12 + K13) + A(2) * K21  + A(3)*K31=

> >
> > DADT(2) = A(1) * K12 - A(2) * K21
> >
> > DADT(3) = A(1) * K13 - A(3) * K31
> >
> > DADT(4)=RT ; TIME ABOVE THRESHOLD TAT
> >
> > DADT(5)=RT*CC ; AUC ABOVE THRESHOLD AUCAT
> >
> > ;----------------- ERROR MODEL ----------------------------------
> >
> > $ERROR
> >
> > IPRED = F
> >
> >    IRES=IPRED-DV
> >
> >    Y=IPRED * (1 + EPS(1)) + EPS(2)
> >
> >    IWRES=IRES/(IPRED * EPS(1) + EPS(2))
> >
> > TAT=A(4)
> >
> > AUCAT=A(5)
> >
> > TIS2 = A(2)/V2
> >
> > TIS3 = A(3)/V3
> >
> > Paul Hutson, PharmD, BCOP
> >
> > Professor
> >
> > UWisc School of Pharmacy
> >
> > T: 608.263.2496
> >
> > F: 608.265.5421
> >
>
>

--
  Alison Boeckmann
  alisonboeckmann_at_fastmail.fm

Received on Wed Jul 31 2019 - 14:03:43 EDT

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