RE: Fx

From: Bachman, William (MYD) bachmanw@iconus.com Subject: RE: [NMusers] Fx Date: Wed, May 26, 2004 8:21 am Katya et al., I think we have beaten one this to death, but, the way I read it, Paul really does want F2 (or the fraction of metabolite "available"), not F1 (the fraction of parent "available"). He has just not done the experiments or collected the appropriate data to get that parameter. I also can't quite yet understand why he wants that parameter or if it even makes any sense. (The metabolite in the central compartment, in my way of thinking, is 100% "available" or is it that Paul is considering that the conversion from parent to metabolite occurs in some other location and we want to know the fraction of the AMT converted in the location that is seen in the central compartment?) This also has confused at least one other person who contacted me off-line. For the record, if you are doing the typical oral and IV experiment (parent only) and you want to estimate bioavailability, you will want to model F1. Nick is correct that DADT(3)was scaled incorrectly for the volume in Paul's original code. Paul would either have to define a new parameter for V3 or else CLME becomes a parameter with units of inverse time (KME). If he chose the former, (identifiability not withstanding): DADT(3)=(A(2)*CLM))/V2-(A(3)*CLME)/V3 My apologies for my contribution to the confusion. Mea culpa. ;) Bill William J. Bachman, Ph.D. Manager, Pharmacometrics Research and Development GloboMax The Strategic Pharmaceutical Development Division of ICON plc 7250 Parkway Drive, Suite 430 Hanover, MD 21076 410-782-2212 bachmanw@iconus.com _______________________________________________________