From: swati j <*swatijaiswal.bhu*>

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

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