How can I correct PK model if I get large RSE on parameter estimates
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*