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The following message was posted to: PharmPK
hi all
it is about WinNonlin Ver.1.5.we have Concentration
time data for a drug and its metabolite after oral
administration of the parent.while fitting metabolite
conc.-time data either by compartmental or
noncompartmental modelling, we have to give the dose
of the drug.while it is fine in case of parent but
what dose value do we need to give in case of
metabolite?
regards
nitin
[If you fit drug and metabolite simultaneously (and are just
administering the drug) you would enter zero as the metabolite dose as
it would be derived from the drug using the right model - db]
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Dear Nitin;
If you are fitting the data simultaneously, then you should write your
model
in such a way that you only need to enter the dose for the parent drug,
as
your model would compute the predicted values for the metabolite (as db
noted). If you are analyzing the data by NCA methods, then WinNonlin
only
uses the dose to compute AUC/D (dose adjusted AUC), which is probably
not a
parameter you need anyway. So you could enter whatever you want for the
metabolite dose when doing NCA. I would not recomment fitting the
metabolite data to a compartmental model (alone) - rather you should
fit it
simultaneously with the parent drug as mentioned above.
Dan Weiner
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The following message was posted to: PharmPK
An example of a technology for modeling formation of a metabolite
from a parent drug you can find in our recent study:
DEDÍK, Ladislav - DURISOVÁ, Mária: System approach
to modeling metabolite formation from parent drug:
A working example with methotrexate. In: Methods and Findings in
Experimental and Clinical Pharmacology 2002,
vol. 24, no. 8, p. 481-486.
The model presented in this study is in a form of a differential
equation,
relating the concentration-time profile of the parent drug and the
concentration-time
profile of the metabolite.
The model allows to determine the metabolic
ratio (as a model parameter), the rate of the metabolite formation, and
the
mean time
of the metabolite formation.
Maria Durisova, PhD, DSc,
Head of Department of Pharmacokinetics
and Scientific Secretary
Institute of Experimental Pharmacology
Slovak Academy of Sciences
841 04 Bratislava 4
Slovak Republic
Phone/Fax: +421 2 54775928
http://www.uef.sav.sk/durisova.htm
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Copyright 1995-2010 David W. A. Bourne (david@boomer.org)