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RE: Modelling intracellular and plasma data

From: Rob ter Heine <Rob.terHeine>
Date: Mon, 15 Dec 2008 15:19:10 +0100

Dear all,

I received some useful suggestions for modelling intracellular pharmacokine=
tics andI'd like to thank everyone who replied in the list or personally. =
Ultimately, visual inspection of my data suggested there was a delay in =
absorption and elimination from the cellular compartment. However, =
individual estimation of these parameters using an effect compartment or =
just plain modelling of intracellular pharmacokinetics independent of =
plasma data, did not improve the model compared to estimation of an =
accumulation ratio.

For future searching purposes I'd like to sum up the suggestions I =
received:

1 - The effect compartment in ADVAN5 (Steven Troy)

 If the PK in the intracellular compartment does not
influence the PK in the plasma compartment (as you stated below), then
you cannot estimate both k23 and k32 independently. I suggest trying
the following modifications.

k32=theta(4); similar to Keo in an effect compartment model
k23=k32*v3/v1

2 - The effect compartment in ADVAN 6 (Nele Plock/Atul Bhattaram/Jacob =
Brogren)

you might try an effect compartmental approach. Use your central
compartment, and then describe the cellular concentrations as being in =
the
effect compartment (the good thing ist that the effect compartment does
not include any mass transfer).

here's the code for a two-compartment model:
 DADT(1)= -K12*A(1)
 DADT(2)= K12*A(1)-K23*A(2)+ K32*A(3) -K20*A(2)
 DADT(3)= K23*A(2)-K32*A(3)
 DADT(4)= KEO1*(A(2)/V2-A(4))

3 - No mass transfer in ADVAN6 (Ron Keizer)

dadt (1) = -ka*a(1)
dadt (2) = ka*a(1) - k20 *a(2)
dadt (3) = k23*a(2) - k32*a(3)

Cheers,

Rob

_______________________________
Rob ter Heine, MSc, PharmD
Department of Pharmacology, Slotervaart Hospital
Amsterdam, The Netherlands
E: rob.terheine
T: +31-20-5124737
Received on Mon Dec 15 2008 - 09:19:10 EST

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