FW: Concentration dependent volume of distribution

From: "Wang, Bing" Subject: FW: [NMusers] Concentration dependent volume of distribution Date: Tue, 19 Mar 2002 09:45:44 -0800 John, This is a loop - the calculation of Conc depends on Vc while in your model Vc is Conc-dependent. It will confuse NONMEM... Most likely the observed conc-dependent Vc is caused by the nonlinear protein binding at (extremely?) low dose levels. A saturable binding compartment (e.g., COMP 2) may be introduced: K12=KON*(RMAX-A(2)) ; RMAX is the maximum number of binding sites. K21=KOFF .... then use K12 and K21 in your DES. It is possible that you have to fix KOFF=1 to avoid overparameterization... Regards. Bing Wang