Re: unidentifiable model

Zhen, I assume you are referring to the common situation of having administered a parent drug with a known dose (but usually unknown extent of bioavailability). Measurements are made of parent and metabolite concentration. Without other information it is impossible to know what fraction of parent is converted to metabolite. There are two choices you can make: 1. Assume all parent is converted to the metabolite. This is like the usual assumption made for oral dosing of the parent. One estimates CL/F and V/F with an unknown value for F. In the case of the metabolite you can estimate CLm/Fm and Vm/Fm where CLm and Vm are the clearance of metabolite and volume of metabolite and Fm is the fraction of the parent converted to metabolite. 2. Fix the metabolite volume of distribution to some value e.g. the same as the parent. If you do this then you can estimate the fraction of parent converted to metabolite (or equivalently the clearance of parent to metabolite plus the clearance by a non-metabolite pathway). I think most people take the first choice. While this is usually not controversial it does mean you have no idea about how much is converted to the metabolite. The second choice requires a guess for the volume of the metabolite but conditional upon that guess you can get some feel for the conversion of parent to metabolite. Nick Zheng Lu wrote: > > Dear all: > > when we model parent and metabolite simultaneously, can we model > fraction of conversion of parent drug to metabolite without any > assumptions to see what fraction is based on the data only? I am > thinking, at this point, estimation of volume of distribution of > metabolite is V/F without any assumptions, F is fraction of conversion. > we don't need know volume of distribution of metabolite exactly because > we want know fraction of conversion first. Once we know the fraction of > conversion(F) after this step, we can model the volume of distribution > of metabolite(V) next exactly. Any instructions will be highly > appreciated. > > Zhen > -- Nick Holford, Dept Pharmacology & Clinical Pharmacology University of Auckland, 85 Park Rd, Private Bag 92019, Auckland, New Zealand [EMAIL PROTECTED] tel:+64(9)373-7599x86730 fax:+64(9)373-7090 www.health.auckland.ac.nz/pharmacology/staff/nholford