Mark,
Thank you very much for your suggestion, we pursued similarly adapted for our
purposes. Two-compartment models were fitted to the separate stereoisomers. The
total concentration was modelled as the sum the differentials for central and
peripheral compartments of the separate stereoisomers. Note that three
different doses must be given in the data set, one for each stereoisomer and
one for the sum.
/ Johan
-----Original Message-----
From: Penney, Mark S
Sent: 19 juni 2008 13:43
To: Rosenborg, Johan
Subject: RE: [NMusers] Joint model fitting to data on separate
enantiomers and enantiomeric mixtures
Dear Johan,
I've used the attached control stream (and data file) to estimate
parameters for a not too disimilar situation.
The model is of the drug (antibody - 2 compartments) and its target ligand. We
measure two things, the free antibody and the so-called total ligand, which is
the summation of the free ligand and that bound to the antibody. This is
measured by an ELISA where the capture antibody recognises an epitope that is
remains available after binding with the therapeutic antibody. I use an IF
statement in the $ERROR block to pick what was measured based on the value of
CMT in the data file.
The aim of the run is to pick up the kinetics of the ligand, which turns over
quite quickly in comparison to the slowly-cleared antibody. I had a mixture of
i.v. and sub-cut administration too.
I used ADVAN8 because it was the only one that could apparently solve the
problem. I had a lot trouble getting NONMEM to run this, hence the simplifying
of all the ETAs fixed to 0.0 and the assumption of the same error for the two
assays. Got what I needed though.
Regards,
Mark
-----Original Message-----
From: [EMAIL PROTECTED]
[mailto:[EMAIL PROTECTED] Behalf Of Rosenborg, Johan
Sent: 18 June 2008 15:28
To: [email protected]
Cc: Johansson, Anna X
Subject: [NMusers] Joint model fitting to data on separate enantiomers
and enantiomeric mixtures
All,
We have a data set comprising three measurements per time point, namely the
separate R- and S-concentrations and the total concentration (R+S) of a chiral
drug given as the racemic mixture. We would like to fit a model to all data
simultaneously. The plan is to estimate one set of parameters for the S-
enantiomer and one set for the R- enantiomer, using the sum of S- and R
concentrations to predict R+S; defining CMTs 1, 3, and 5 as observational
compartments for R-, S-, and RS, respectively, we would like to model
A(5)=A(1)+A(3). Any suggestion on how to do proceed with this in ADVAN5 or
ADVAN6 would be appreciated!
/ Johan and Anna
