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residual variability

From: Sultan,Abdullah S <a3bdu3>
Date: Tue, 27 Sep 2016 17:12:57 +0000

Hi everyone,

I have a rich data set for a drug administered orally. The drug has slow ab=
sorption (Tmax 4 hours) and rapid elimination (2 hours half life). A tlag m=
odel was sufficient to describe the data but I ran into difficulties with t=
he error model.

If I use a proportional or combined error model, the model is unstable and =
I get unrealistic estimates (very large Vd, Cl and residual variability) . =
It is only stable if:

1) I use a constant error model

2) Use a combined error model and fix the a part

When I use a constant error model, the diagnostic plots clearly show the er=
ror is not constant

Not sure what the cause for this is, I tried several things to fix it like =
changing initial estimates or structural model (transit compartment, zero o=
rder,....), deleting outliers or low concentrations near the BLQ but the pr=
oblem still persists.

Any suggestions


Abdullah Sultan

Received on Tue Sep 27 2016 - 13:12:57 EDT

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