RE: Simultaneous drug and metabolite POPPK

Mike, This depends on the purpose of the modeling and the information available. Usually, we only have Parent and Met concentration data after oral administration, therefore, we can't estimate the true disposition parameters. We can get CL/F and V/F for parent, but we can get nothing more than apparent Production rate constant and Elimination rate constant for Met. In this case, converting the data to micromolar unit or not is not critical. e.g. Let's begin from the differential equation below: DADT(3)=KMP(iv)*A(2)-KME*A(3) Eq 1 where A(2) is the amount of parent (mg), A(3) is the amount of metabolite (mg). KmP is the production rate of the metabolite. Because the distribution volume of Met (V3) is unobtainable (no IV data of Met), we have to convert dA/dt to dC/dt and divide both sides of Eq 1 by V3 as follows: DADT(3)/V3=KMP(iv)*A(2)/V3-KME*A(3)/V3 Eq 2 In NONMEM, we coded this as follows: DADT(3)=KMP *A(2)/V2-KME*A(3) Eq 3 Please note that DADT(3) in Eq 3, actually, is dC3/dt (a rate of concentration instead of amount), and KMP in Eq 3 = KMP(iv) x V2/V3 in Eq 1. In other words, KMP is a composite parameter of both volumn ratio and molecular weight ratio. If there are IV data for both parent and metabolite after administrations of parent and metabolite seperately, the true disposition parameters can be estimated for both. By converting the concentration unit to molar, we can estimate formation fraction of parent to metabolite. Jun Shi Clinical Pharmacology and Drug Dynamics Forest Research Institute Rm18-35 Harborside Financial Center-Plaza V Jersey City, NJ 07311 Tel: 201-427-8044 Fax: 201-427-8498 Email: [EMAIL PROTECTED] -----Original Message-----