RE: metabolite modeling

From: "Piotrovskij, Vladimir [JanBe]" <VPIOTROV@janbe.jnj.com> Subject: RE: metabolite modeling Date: Fri, 17 Dec 1999 08:39:00 +0100 Steve, Your last argument seems convincing. However, I am still not sure the LINEAR composite model developed on the basis of single-dose data will produce wrong predictions for multiple dosing. The situation has to be tested by simulations/fittings. As to the NONLINEAR case (the effect of metabolite on the parent is an example), it is totally different from the LINEAR one. In general, nonlinear systems have less identifiability problems as compared to linear systems. For instance, if metabolite inhibits its own formation, you can estimate its ke even having no metabolite concentration measured at all. I showed the relevant example during the last NONMEM workshop in Uppsala. Also, the "first-pass" case becomes much simpler if the kinetics of metabolism is saturable. Best regards, Vladimir ---------------------------------------------------------------------- Vladimir Piotrovsky, Ph.D. Janssen Research Foundation Clinical Pharmacokinetics (ext. 5463) B-2340 Beerse Belgium Email: vpiotrov@janbe.jnj.com