Re: [NMusers] How can I correct PK model if I get large RSE on parameter estimates

From: swati j <swatijaiswal.bhu_at_gmail.com>
Date: Mon, 25 Jan 2016 12:41:02 +0530

Dear Dr.Ayyappa

Thanks for suggestion. You were right. I checked the model without RUV and
found that model run successfully without any error message. Minimization
was successful with OFV value of 501.08 (OFV of previous run 477.71). Also
I observed that there was no significant difference in the parameter
estimates and basic GOF plots from previous model (both additive and
proportional RUV) and current model (proportional RUV only). I think now it
is crystal clear that additive RUV was not required.

thankyou

Best Regards,
Swati


Swati Jaiswal

PhD Scholar (CSIR-Senior Research Fellow)

Pharmacokinetics & Metabolism Division

CSIR-Central Drug Research Institute

*Lucknow-226031, India*

*Mobile +91 9473837970*

On Fri, Jan 22, 2016 at 3:06 AM, Ayyappa Chaturvedula <ayyappach_at_gmail.com>
wrote:

> Swati,
>
> Did you run a model without additive RUV and checked if it is required?
>
> Best Regards,
> Ayyappa
>
> On Jan 21, 2016, at 2:44 AM, swati j <swatijaiswal.bhu_at_gmail.com> wrote:
>
> Dear members of nmusers:
>
> I am trying to do PopPK analysis of plasma concentration-time data obtained from a non-steady-state PK study of a drug in hamsters (at 2 doses; 10 mg/kg and 20 mg/kg, p.o for 5 consecutive days at interval of 24 hr).
>
> after executing the model file(one compartment model with first order absorption), the result indicated successful minimization, but with one WARNING messgae :
>
> "*Large relative standard errors found, *
>
> *additive RUV 0.363451"*
>
> Please suggest What should I do next?....How I can reduce the RSE and what should be my next step to improve the model
>
> the model file which i used is as follows
>
> $PROBLEM PK model 1cmt
>
> $INPUT ID TIME DV AMT ADDL II MDV
> $DATA paginPK4.csv IGNORE=#
> $SUBROUTINE ADVAN2 TRANS2
> $PK
> KA=THETA(1)*EXP(ETA(1))
> CL=THETA(2)*EXP(ETA(2))
> V =THETA(3)
> SC=V/1000
> STRT = 0
> $THETA (0,0.338111) ; KA
> (0,11.4608) ; CL total
> (0,1049.2) ; V2
> $OMEGA 0.0423895 ; KA
> 0.0143127 ; cl
> $SIGMA 0.0640523 ; proportional RUV
> 0.00105349 ; additive RUV
> $ERROR
> IPRED = F
> IRES = DV-IPRED
> W = DV
> IWRES = IRES/W
> Y = IPRED*(1+EPS(1)) + EPS(2)
>
> $ESTIMATION METHOD=1 INTERACTION MAXEVAL=9999 SIG=3 PRINT=5 NOABORT
> POSTHOC
> $COVARIANCE PRINT=E
> ;$SIM (1234) NSUBPROBLEMS=1 ONLYSIM
> $TABLE ID TIME DV PRED IPRED RES WRES IRES IWRES CL V KA AMT DV
> NOAPPEND NOPRINT ONEHEADER FILE=out8.tab ; Xpose
> $TABLE ID TIME DV IPRED IRES IWRES CWRES NOPRINT ONEHEADER
> FILE=sdtab8
> $TABLE ID KA CL V NOPRINT ONEHEADER FILE=patab8
> $TABLE ID NOPRINT ONEHEADER FILE=cotab8
> $TABLE ID NOPRINT ONEHEADER FILE=catab8
>
> thanks in advance
>
>
> Regards
>
> Swati
>
> Swati Jaiswal
>
> PhD Scholar (CSIR-Senior Research Fellow)
>
> Pharmacokinetics & Metabolism Division
>
> CSIR-Central Drug Research Institute
>
> *Lucknow-226031, India*
>
> *Mobile +91 9473837970 <%2B91%209473837970>*
>
>

Received on Mon Jan 25 2016 - 02:11:02 EST

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