Re: 2 comp MM

From: "Nick Holford" <n.holford@auckland.ac.nz> Subject: Re: 2 comp MM Date: Fri, 11 Dec 1998 09:30:03 -0800 My 2c on parameterization of capacity limited elimination models (aka MM, saturable, non-linear): If Vmax is parameterized as conc/time instead of amount/time then it is necessarily confounded with the volume of distribution. This is similar to the problem of parameterizing a model in terms of a half-life or rate constant. When describing the concs in an individual the parameterization is irrelevant but when trying to estimate population model parameters the conc/time parameterization of Vmax will introduce covariance between Vmax and volume that is a consequence of the parameterization rather than reflecting some underlying biology that one might be interested in exploring. As Bill Bachman has pointed out it is a matter of personal preference ("intuitiveness") which one uses but I am on the side of amount/time as well as the CL, V [Q,Vss] parameterizations instead of half-lives, micro-constants and God Forbid A,B,alpha and beta (Watch out Kinetica!). My rational, as opposed to intuitive, argument is to try and have parameters reflect independent properties of the underlying biology and avoid confounding if possible. -- Nick Holford, Dept Neurology,L226 OHSU, 3181 SW Sam Jackson Park Rd, Portland,OR 97201,USA email:n.holford@auckland.ac.nz tel:+1(503)494-7228 fax:494-7242 http://www.phm.auckland.ac.nz/Staff/NHolford/nholford.htm