NONMEM Users Network Archive

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Age effect on Clearance

From: Mona.Alameddine
Date: Tue, 15 Dec 2009 14:53:50 +0100

Dear nmusers,

I am getting funny results when i add age as a covariate on oral clearance:
The OF decreases by 16 points,
but :
BSV on CL increases from 35% to 37%
BSV on V decreases from 49% to 47%
Intra-Individual variability decreases from 41% to 38%

And the most important is that the age had a positive effect on CL
Where CL INCREASED with age (THETA2 = -0.37 ). Age is not correlated
to other covariates and remained significant in the final model
together with the body weight.
I also tried several ways to test the effect of age , but NONMEM
didn't converge.

I also had funny results when i tried FOCE-I method, because i got a
very small variability on oral CL (0.7%) though i had much lower OF
(-55 points)
and the Covariance step failed.


I used the following:

$SUB ADVAN2 TRANS2

$PK
MAGE = 40 ; Median age
FAGE = (AGE-MAGE)/MAGE ; Fractional effect of age
TVCL = THETA(1)* (1- THETA(2)*FAGE)
CL = TVCL * EXP (ETA(1))
V = THETA(3)* EXP (ETA(2))
KA = THETA(4)
F1 = THETA(5)

S2=V/1000

$THETA (0,10)(0.5)(0,100)(0,0.6)(1 FIX)

$OMEGA 0.5 0.5

$ERROR
Y=F*EXP(ERR(1))
IPRED=F
IRES=DV-IPRED
W=F; if err prop W=F else W=1
IWRES=IRES/W


$SIGMA 0.5

$ESTIMATION SIGDIGITS=3 METHOD=1 MAXEVAL=9999 NOABORT POSTHOC PRINT=1

$TABLE UNCONDITIONAL ID TIME AMT CL V KA DV PRED IPRED IRES RES WRES IWRES
AGE SEX BW HGT ETA1 ETA2 EVID NOPRINT ONEHEADER FILE=run08.table.txt


Any suggestions on how to handle these results??

Thank you in advance for your help

Mona
Received on Tue Dec 15 2009 - 08:53:50 EST

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