Re: Endogenous drug

From:eonid Gibiansky Subject:Re: [NMusers] Endogenous drug Date:Fri, 12 Jul 2002 09:00:26 -0400 Sophie, To place a constant amount in any compartment you need to have a source (a steady-state infusion-type input into some compartment) that would results in the appropriate endogenous level. I am not sure that you need this complication. I your model, you do not add addition amount to the central compartment but subtract (from DV) the endogenous concentration level. (The description: > In above case, >NONMEM code only adds to the amount (once) in the central compartment >(CBAS) ignoring the peripheral compartment. is not quite correct) Assuming linearity, you model "extra dose", ignoring natural level. If you really need endogenous levels in the other compartments, you may look for a steady-state solution of the system that you find in your modeling process. For sure, concentrations in the other compartment can be expressed via the model parameters and endogenous level in the central compartment (assume that all DADT=0). You also may find corresponding source (as a free term in the equation for the central compartment if the source is in the central compartment). For a two compartment model, equations for the "endogenous part" of the concentration are as follows: DA1DT=p1-(k12+k10) A1+k21 A2 DA2DT=k12 A1 - k21 A2 where p1 is "endogenous source", A1, A2 are endogenous amounts (A1=CBAS*V1) Assuming DA1DT=DA2DT=0, A2 (or C2) and p1 can be expressed as a function of CBAS and model parameters. Of course, if you have reasons to believe that your endogenous source is in the compartment 2, you will need to solve for -(k12+ k10) A1+k21 A2 = 0 k12 A1 - k21 A2+p1=0 Leonid