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Modelling intracellular and plasma data

From: Rob ter Heine <Rob.terHeine>
Date: Tue, 09 Dec 2008 14:27:32 +0100

Dear all,

I'm trying to fit concentrations of a drug simultaneously measured in =
plasma as well as intracellularly (in peripheral blood mononuclear cells). =
I observe a high accumulation in cells, but with a delayed absorption. I'm =
trying to fit the intracellular data dependent of the plasma pharmacokineti=
cs. The volume of distribution of the cellular compartment can be =
considered negligeble compared to the volume of distribution in plasma (no =
distribution to a second compartment can be observed in the plasma =
pharmacokinetics. However, cellular accumulation depends on plasma =

I'm fitting the data with a first order oral absorption and elimination, =
basically it can be summarized as:


I have a rich sampling dataset of 11 individuals with at each timepoint an =
observation in the cellular and plasma compartment. I have tried several =
approaches for modelling cellular accumulation. I have tried fixing the =
cellular volume to a very small volume.


This didn't work. K23 was estimated to be very small and k32 was estimated =
to be very large, giving the same fit as estimating an accumulation ratio, =
which is not a good fit, since a delayed absorption in the cellular =
compartment was observed. There is some mass transport going on between =
the central and cellular compartments, that I do not want. My cellular =
pharmacokinetics depend on the plasmapharmacokinetics, but I don't want my =
cellular pharmacokinetics to influence my plasma pharmacokinetics, since =
this effect is likely negligible. Does anyone have a smart idea on how to =
code this?


Rob ter Heine

Rob ter Heine, MSc, PharmD
Department of Pharmacology, Slotervaart Hospital
Amsterdam, The Netherlands
E: rob.terheine
T: +31-20-5124737
Received on Tue Dec 09 2008 - 08:27:32 EST

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