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Question about mixture model of Ka

From: Xu, Claire <smartxucong>
Date: Mon, 23 Jul 2012 14:44:32 -0400

Hi Dear nmusers,

I am trying to develop a pop PK model. In my data, there are two
subpopulations, one subpopulation with Ka of about 9 and the other one with
Ka of about 1. The percentage of population with higher Ka is about 15%. I
assumed that it would be reasonable to utilize mixture model of Ka. But I
cannot get the mixture model of Ka successfully run under NONMEM, because
the percentage of the subpopulation can't be estimated. Can anyone help
check my NONMEM code? Is there anything special that I should do for the
input data profile? .I will very appreciateit it for your generous help.
Thanks a lot!
Claire

$SUB ADVAN2 TRANS2
$PK
CL=THETA(1)*EXP(ETA(1))
V=THETA(2)*EXP(ETA(2))
EST=MIXEST
IF (MIXNUM==1) THEN ; pop1
   KA=THETA(3)*EXP(ETA(3))
ELSE
   KA=THETA(4)*EXP(ETA(4)) ; pop2
ENDIF
S2=V/1000 ; convert concentration to ng/ml
$MIX
NSPOP=2
A=EXP(THETA(5))
DEN=1+A
P(1)=1/DEN ;pop1
P(2)=A/DEN ;pop2
$ERROR
DEL = 0.0001
IPRED = LOG(DEL)
IF (F.GT.DEL) IPRED = LOG(F)
W=THETA(6)
IRES=IPRED-DV
IWRES = IRES/W
Y=IPRED+EPS(1)*W
$THETA
(0,50) ;CL
(0,550); V
(0,1.5);KA for pop 1
(0,6); KA for pop 2
(0,1); per
(0,0.16);W
$OMEGA BLOCK(2)
0.16
0.01 0.16
$OMEGA
0.16
0.16
--
Xu, Claire
Ph.D Candidate
Division of Clinical Pharmacology, Wishard Hospital
Indiana University School of Medicine
1001 West 10th Street, Myers W7122
Indianapolis, IN 46202
T - 317/7558242

Received on Mon Jul 23 2012 - 14:44:32 EDT

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