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

From: swati j <swatijaiswal.bhu_at_gmail.com>
Date: Thu, 21 Jan 2016 14:14:53 +0530

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*

Received on Thu Jan 21 2016 - 03:44:53 EST

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