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RE: Joint model fitting to data on separate enantiomers and enantiomeric mixtures

From: Rosenborg, Johan <Johan.Rosenborg>
Date: Tue, 24 Jun 2008 17:13:40 +0200


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.


-----Original Message-----
From: owner-nmusers
Sent: 18 June 2008 15:28
To: nmusers
Cc: Johansson, Anna X
Subject: [NMusers] Joint model fitting to data on separate enantiomers
and enantiomeric mixtures


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
Received on Tue Jun 24 2008 - 11:13:40 EDT

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