Re: metabolite modeling

Date: Fri, 10 Dec 1999 13:10:33 +0100 From: Mats Karlsson <Mats.Karlsson@biof.uu.se> Subject: Re: metabolite modeling "HUTMACHER, MATTHEW" wrote: > Sequential fitting of the data (fitting the parent first, assessing the fit, > if it fits well fixing the parameters for the metabolite fit and then > fitting the metabolite) helps me cut down run time for the "getting to know > the data" portion of modeling. Especially with complicated models and > differing administration routes. I would agree that sequential fitting is useful during model building. For drug-metabolite models, I would however, once the structural models have been selected, look into parameter correlations between drug and metabolite. These may provide information on e.g. magnitudes of metabolic pathways (even if they can be difficult to interpret sometimes). Also, metabolite data oftentimes contain information about parameters of the drug model, for example when the terminal half-life of the metabolite is the same as for drug, due to elimination rate limitation. Thus, doing sequential analysis for drug-metabolite PK data is more questionable than for PK/PD data (where PD data seldom contain much info about the PK). Mats