Re: Parameterization!!!

From: Nick Holford <n.holford@auckland.ac.nz> Subject: Re: Parameterization!!! Date: Thu, 10 May 2001 12:06:28 +1200 The elimination rate constant has no independent physiological correlate in the body if you are trying to describe drug concentrations. Volume of distribution and clearance have clear physical analogues. There are also well understand relationships which affect V and CL e.g. body size, renal function, in different ways so that the ratio CL/V (which defines the elimination rate constant for a 1 cpt model) is not a constant if one compares different people. A major application of popln PK analysis is to discover and describe these differences between people. Parameterizing your model in terms of an elimination rate constant rather than CL and V will only make things harder to understand if you introduce covariates to predict differences in CL and V. It gets much more difficult if you want to use a 2 compartment model. So my advice is to keep things simple and learn to think in terms of clearance and volume and not in terms of rate constants (which are not constant!). Nick -- Nick Holford, Divn Pharmacology & Clinical Pharmacology University of Auckland, 85 Park Rd, Private Bag 92019, Auckland, New Zealand email:n.holford@auckland.ac.nz tel:+64(9)373-7599x6730 fax:373-7556 http://www.phm.auckland.ac.nz/Staff/NHolford/nholford.htm