RE: Question about mixture model of Ka
Dear Claire,
Through your constraint on THETA(5), you have restricted the mixture model
to have MIXNUM=2 as the dominating (>=50%) subpopulation. I think this may
result in your run ending up in a local minimum. I wouldn't be surprised if
THETA(5) is driven towards zero. If you want to keep this parameterization
for P(1), maybe you should try switching initial est's between THETA3 and
THETA4.
Best regards,
Mats
Mats Karlsson, PhD
Professor of Pharmacometrics
FIRST WORLD CONFERENCE ON PHARMACOMETRICS, 5-7 September 2012, Seoul (
http://www.go-wcop.org/ www.go-wcop.org)
Dept of Pharmaceutical Biosciences
Faculty of Pharmacy
Uppsala University
Box 591
75124 Uppsala
Phone: +46 18 4714105
Fax + 46 18 4714003
Quoted reply history
From: [email protected] [mailto:[email protected]] On
Behalf Of Xu, Claire
Sent: 23 July 2012 20:45
To: [email protected]
Subject: [NMusers] Question about mixture model of Ka
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 <tel:317%2F7558242>