RE: 2 compartment MM

From: "Bachman, William" <bachmanw@globomax.com> Subject: RE: 2 compartment MM Date: Fri, 11 Dec 1998 09:15:42 -0500 Dr. Bonate is correct, of course, with repsect to "mathematical identifiability" of the parameters of parallel elimination models from central & peripheral compartments. (In the model code distributed, both elimination paths are from the central compartment). Physiologically, it is not uncommon to have more than one elimination route, one of which is nonlinear. (e.g. a metabolic path & renal elimination. The question is - does your data support your model? (and does your model accurately describe your data) In practice, I have found that it's often less difficult to fit the parallel model to data than a nonlinear only model. For an example, see: Bachman, W. J., and DeLap, R. J., "Population Pharmacokinetics of High-Dose Zidovudine in a Phase I Cancer Study", Drug Invest., 8(3), pp. 134-142 (1994). With respect to the comments on the parameterization of Vm & Km (R.E. Port), yes, there is more than one way to parameterize Michaelis-Menten kinetics. I find the one I use more intuitive (to me). One should just be consistant (and aware) of which you are using. William J. Bachman, Ph.D. GloboMax LLC Senior Scientist 7250 Parkway Drive, Suite 430 Hanover, MD 21076 Voice (410) 782-2212 FAX (410) 712-0737 bachmanw@globomax.com