Need advice

From: clement clement@ha.mc.ntu.edu.tw Subject:[NMusers] Need advice Date: Tue, April 27, 2004 9:24 pm Dear NONMEM users: Regarding the unit of Km in ADVAN6 and ADVAN10, quite a few discussions have been posted in NONMEM Users Network. Although so far our lab have the lucky experience to have a successful case by using both subroutines, I have been contemplating this old question for some time, and I wonder if any one could kindly help me to further clarify the following questions. First, in ADVAN6, it is recommended to define C2=A(2)/S2 along with dA/dt = -C2*Vm/(Km+C2) to have Km unit of concentration. One possible reason has been proposed in 1995 as the following: " ....But within the $DES block, unscaled compartment amounts are present in the variables A(1), A(2), A(3), etc. This is why A(2)/S2 (a concentration) was computed for use in the M-M elimination term -C2*VM/(KM+C2)... " It is no problem to use "amount" and "time" for R (or dA/dt) because those are what we input in the data file. However, what we input for the DV (dependent variable) are usually in the unit of "concentration". Does "NONMEM" internally multiply the DV (in a unit of concentration) by volume to have a unit of amount in A(2) so that we have to re-scaled it again by defining A(2)/S2 in $DES block (as well as it is used as F=A(2)/S2 in $ERROR)? Or, just like what has been told by Dr. Joachim Grevel: " Since she defines the CENTRAL compartment as DEFOBS, the line > C2 = A(2)/S2 in $DES is redundant ..." Likewise, in ADVAN10, it is known that ADVAN10 uses amounts rather than concentrations in its computations. Regardless of its physiological meaning, again, does "NONMEM" internally multiply the DV (in a unit of concentration) by volume to have a unit of amount in A(2) to be used in -A(2)*VM/(KM+A(2))? If so, where does "NONMEM" find the value of volume to be multiplied? Any help would be much appreciated! CJ Lin, College of Medicine, NTU _______________________________________________________