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Hi all,
I have a problem with the modeling on WinNonLin.
I have done a program 3 compartments oral with macroconstants. I have
to model repeated doses and single dose data.
When I model repeated doses data, I obtain macroconstants and
microconstants (as secondary parameters). When I model single dose
data, I obtain microconstants which are similar to the values obtain
with repeated doses but macroconstants are very different.
And when I want to make predictions, the macroconstants obtained with
repeated doses data give logic concentrations whereas macroconstants
obtained with single dose data give totally abnormal concentrations.
Is there an explanation?
Thank you
C. Gesson
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The following message was posted to: PharmPK
Charlotte
What you call macroconstant corresponds in fact to an ensemble of
terms that differs from a single dose to a multiple dose situation by
the accumulation factor for each exponential term. This depends on
the corresponding rate constant and on the dosing interval, 1/(1-exp(-
k*tau)) in steady-state. The microconstants are naturally not
affected since the kinetics doesn't change.
On the side, please notice that there's a difference between a 3
compartmental model with first order absorption (4 exponential terms)
and a 3 exponential model with first order absorption (2 disposition
compartments).
Hope this helps
Luis
--
Luis M. Pereira, Ph.D.
Assistant Professor, Biopharmaceutics and Pharmacokinetics
Massachusetts College of Pharmacy and Health Sciences
179 Longwood Ave, Boston, MA 02115
Phone: (617) 732-2905
Fax: (617) 732-2228
Luis.Pereira.at.bos.mcphs.edu
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Hi,
Macro constants in WinNonlin are dependent of stripping dose (dose)
and so if you normalize these to your dose you will be able to
predict your response at unit dose level and change accordintly to
your dose, as you do in deconovolution.
Hope this helps,
Ayyappa Chatrvedula
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