Re: metabolite modeling

From: "Stephen Duffull" <sduffull@fs1.pa.man.ac.uk> Subject: Re: metabolite modeling Date: Thu, 16 Dec 1999 09:13:18 -0000 Vladimir > The model that has just been discussed is a simplest one: > the metabolite of interest is formed only systemically (i.e., no > "first-pass" metabolism). I agree that the case was simplier than one that includesconsideration of first-pass metabolism. Having said that it remains possible to retain a globally identifiable model even under these circumstances, although it does require some parameters to be fixed (at prior or arbitrary values). If this is done the model may not retain biological exactness with respect to the fate of the drug (eg you may have to assume that the drug is only absorbed intact or converted to one metabolite on first-pass) - but nevertheless will reflect the observed data accurately. > And I ask myself: why do we need a full model? If the goal is to obtain a > good approximation for the parent drug and the metabolite plasma > concentration profiles that can be used for predictions (say for further > PK-PD modelling) why not to fit independent models to the parent drug curve > and the metabolite curve? If you fit independent models not only do you have almost all of the assumptions of fitting a full model but you eliminate the influence of metabolite on the parent (which as has been discussed by Mats and Leon is important), and also importantly the influence of changes in input variables or parent PK on metabolite PK. Where possible the full model, even under various assumptions, would seem preferable. Regards Steve ===================== Stephen Duffull School of Pharmacy University of Manchester Manchester, M13 9PL, UK Ph +44 161 275 2355 Fax +44 161 275 2396