RE: log transformed data and multi compartment PK

From: "Gordi, Toufigh" Toufigh.Gordi@cvt.com Subject: RE: [NMusers] log transformed data and multi compartment PK Date: Tue, 26 Jul 2005 15:29:23 -0700 Hi Immo, Your model is a very complex one: a drug with 2-compartmental kinetics (compartments 1 and 3 in your model) with 2 distinctive elimination pathways: one forming a measured metabolite (compartment 2) and another with a rate of KE. Your model also implies that the metabolism is reversible and beside being eliminated by a rate of KKX, the metabolite is also transformed back to the parent compound. Maybe I understand you incorrectly but I thought you were trying to fit a 1-comp model to your data. Assuming the model is correct as written, it is indeed quite complex and unless you have very good data it would be difficult to estimate all the parameters of the model. On the top of that, you are trying to estimate not less than 8 variability terms! My suggestion to you is to start with the simplest model you can come up with (which at the same time is supported by what you know about your compound and its metabolite), trying to estimate 1-2 ETAs at the most. Once you have established the simple model, you can add more complexity by adding more structural model and /or variability parameters. I also recommend that you name the parameters after the compartments to make it easier for others to follow your model. I am assuming that you have a metabolite with longer elimination half-life, or you know the kinetics of your metabolite after an iv dose of the metabolite from previous studies. Otherwise, you will have difficulties in estimating model parameters associated with your metabolite. Others have already addressed the problem with log-normalized data. Toufigh Gordi