Modelling intracellular and plasma data

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 pharmacokinetics. 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 concentrations. I'm fitting the data with a first order oral absorption and elimination, basically it can be summarized as: $Model (DOSE) (CENTRAL) (CELL) 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. $PK k12=theta(1) v1=theta(2) cl=theta(3) k20=cl/v1 v3=0.0001 k23=theta(4) k32=theta(5) 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? Sincerely, Rob ter Heine _______________________________ Rob ter Heine, MSc, PharmD Department of Pharmacology, Slotervaart Hospital Amsterdam, The Netherlands E: [EMAIL PROTECTED] T: +31-20-5124737