From: Weijiang Zhang <ZHANGW@mail.rx.uga.edu>
Subject: Help: oral and ig bioavailability by NONMEM
Date: Tue, 28 Aug 2001 02:46:10 GMT
Dear NONMEM users:
When I tried to use NONMEM to analyze my data, there is a
problem I don't know how to do with it. My study is about
giving a compound to six subjects by three different
administration routes: iv, ig and oral. I used subroutines
ADVAN4 TRANS3, that's two compartment with first order
absorption. Everything works out fine except the
bioavailability.
Following is my code for absorption rate (KA)(the
absorption is rapid for both routes) and bioavailability:
$PK
X1=0
X2=0
IF (WZ.EQ.1) THEN ;WZ is the indicator, WZ=1, oral dose
X1=1
ENDIF
IF(WZ.EQ.2) THEN ;WZ=2, ig dose
X2=1
ENDIF
KA = X1*THETA(5) + X2*THETA(6)
TVF1 = X1*THETA(7) + X2*THETA(8)
F1=TVF1 *(1+X1*ETA(2)+X2*ETA(3)) + (1-X1-X2)*THETA(9)
Most parameters are well estimated, however, the F1 for oral
(theta7) was estimated to be 1.52, for ig (theta8) was 0.58,
which were very different from the number (0.95 and 0.70) I
got by noncompartmental analysis using Winnonlin. I've
already double checked my data set to make sure it's
correct.
My first question is: Is that right to use F1 here? or F2?
Second: Is my code correct to estimate bioavailability for
oral and ig in this model? What can I do to get the "right"
estimation?
Any help will be highly appreciated.
Thank you so much for your time and attention.
Sincerely,
Weijiang Zhang
UGA
Help: oral and ig bioavailability by NONMEM
From: "Rik Schoemaker" <RS@chdr.nl>
Subject: Re: Help: oral and ig bioavailability by NONMEM
Date: Tue, 28 Aug 2001 10:09:33 +0200
Dear Weijiang,
I'm a bit puzzled about your THETA(9) parameter; it seems to be=20
related to "bioavailability" for the IV dose (when both X1 and X2=20
are 0) which however should not operate on compartment 1 because=20
the IV dose is introduced in compartment 2...Why is it there?
Could you try and see if the following syntax produces correct results
(after checking that the IV dose indeed enters comp2):
instead of:
TVF1 =3D X1*THETA(7) + X2*THETA(8)
F1=3DTVF1 *(1+X1*ETA(2)+X2*ETA(3)) + (1-X1-X2)*THETA(9)=20
use:
F1=3D X1*THETA(7)*(1+ETA(2)) + X2*THETA(8)*(1+ETA(3))
and drop THETA(9)...
Did you try using FOCE estimation with interaction?
Good luck,
Rik
Rik C. Schoemaker, PhD
Biostatistician - pharmacokineticist
Centre for Human Drug Research (CHDR)
Zernikedreef 10, 2333CL Leiden, Netherlands
tel +31 (0) 71 5246417; fax +31 (0) 71 5246499
email rs@chdr.nl; http://www.chdr.nl
From: "Piotrovskij, Vladimir [JanBe]" <VPIOTROV@janbe.jnj.com>
Subject: RE: Help: oral and ig bioavailability by NONMEM
Date: Tue, 28 Aug 2001 12:37:24 +0200
Weijiang,
I agree with Rik: THETA(9) seems to be redundant. Another potential problem:
too few individuals. You cannot estimate so many random effects having only
6 subjects. Fixed effect estimates can also be affected. I think you have to
fit each subject separately. Interoccasion variability should be taken into
account, too.
Best regards,
Vladimir
Centre for Human Drug Research (CHDR)
Zernikedreef 10, 2333CL Leiden, Netherlands
tel +31 (0) 71 5246417; fax +31 (0) 71 5246499
email rs@chdr.nl <mailto:rs@chdr.nl> ; http://www.chdr.nl
http://www.chdr.nl