RE: time-dependent clearance model
Hi Jeet,
Thanks for the advice. I got the initial guess of KIN from previous studies
which believe that the maximum induction occurs at day 7. So I let clearance at
168 hrs be equal to 98% of steady stage clearance (CLSS) and by using initial
guesses of CLI and CLSS, the initial guess of KIN was calculated as 0.02. The
clearance is induced. It increases with time instead of decreasing. How should
I determine if my model is over-parameterized?
Thank you.
Best,
Xiaofeng
Quoted reply history
________________________________
From: Isingh716 [[email protected]]
Sent: Sunday, March 04, 2012 7:22 PM
To: Wang, Xiaofeng
Subject: Re: [NMusers] time-dependent clearance model
How do you know the initial guess of KIN ? Right now it is 0.02 which will mean
~40-50hr for CL half life (so to imagine) you think it's reasonable for CL to
drop by that much in 50hrs ? You can possibly try different initial guesses for
KIN and see how does system react to ? Look for correlation and see if you are
not over parametrizing the model.
Best
Jeet
Sent from my iPhone
On Mar 4, 2012, at 4:33 PM, "Wang, Xiaofeng"
<[email protected]<mailto:[email protected]>> wrote:
Dear nmusers,
I have a drug with clearance autoinduction. I have sparse data(three
observations on day 1, two between day 7 and 14, and one on day 28). I am
trying to run a time-dependent clearance model. I tried FO and FOCEI, but I
always got unreasonable estimate for the initial clearance (CLI) which is about
0.15 L/h (from knowledge of previous studies, the reasonable initial clearance
should be around 20 L/h and maximum induction occurs around day 7). Could
someone give me some advice about my model and my data? Thank you.
Xiaofeng
The CTL file:
$PROB
$INPUT C ID TIME AMT DV MDV EVID ADDL II CMT
$DATA C:/ IGNORE=C
$SUBROUTINES ADVAN6 TOL=6
$MODEL NCOMPARTMENTS=3
COMP=(DEPOT,DEFDOSE)
COMP=(CENTRAL,DEFOBS)
COMP=(PERIP)
$PK
CLI=THETA(1)*EXP(ETA(1))
CLSS=THETA(2)*EXP(ETA(2))
KIN=THETA(3)*EXP(ETA(3))
V2= THETA(4)*EXP(ETA(4))
Q= THETA(5)*EXP(ETA(5))
V3= THETA(6)*EXP(ETA(6))
KA= THETA(7)*EXP(ETA(7))
S2=V2
K23=Q/V2
K32=Q/V3
$DES
CL=CLSS-(CLSS-CLI)*EXP(-KIN*T)
K20=CL/V2
DADT(1)=-KA*A(1)
DADT(2)=KA*A(1)+K32*A(3)-K23*A(2)-K20*A(2)
DADT(3)=K23*A(2)-K32*A(3)
$ERROR
IPRE=LOG(1)
IF(F.GT.0) IPRE=LOG(F)
Y = IPRE+EPS(1)
$EST METHOD=0 POSTHOC PRINT=10 MAX=9999 SIG=2 NOABORT MSFO=050.MSF
$THETA
(0, 20);[CLI]
(0, 65);[CLSS]
(0, 0.02) ;[KIN]
(0, 45);[V2]
(0, 5);[Q]
(0, 58);[V3]
(0, 0.2);[KA]
$OMEGA .25 .25 .25 .25 .25 .25 .25
$SIGMA .2
$COV PRINT=E
$TABLE ID TIME DV CLI CLSS KIN V2 Q V3 KA IPRE CWRES ONEHEADER NOPRINT
FILE=050.TAB
$TABLE ID TIME CLI CLSS KIN V2 Q V3 KA FIRSTONLY NOAPPEND NOPRINT FILE=050.PAR
$TABLE ID ETA1 ETA2 ETA3 ETA4 ETA5 ETA6 ETA7 FIRSTONLY NOAPPEND NOPRINT
FILE=050.ETA
$TABLE ID TIME CLI CLSS KIN V2 Q V3 KA FIRSTONLY NOAPPEND NOPRINT FILE=PATAB050