Re: Covariate Models Using Weight

Date: Tue, 23 Nov 1999 09:34:45 +1300 From: Nick Holford <n.holford@auckland.ac.nz> Subject: Re: Covariate Models Using Weight James Gallo wrote: > Nick, > > I feel you also are missing my point about covariate modeling related to > renal function or any other mechanism related to drug disposition. For > some reason you seem to want to adhere to PRE-DEFINED Formulas to describe > CRCL and subsequently drug clearance. PRE-DEFINED = prior knowledge As Lewis Sheiner has pointed out we can always test using a Bayesian formulation if our data really has something to add to what we know already. I like to use prior knowledge if possible because in information about covariate relationships is usually sparse. > Given the problem of developing a population model for DRUG X that undergoes > appreciable renal clearance, I believe it is more rational to start from > scratch. That is your choice. I prefer to lean on all the scientific knowledge we have accumulated to date rather than reinvent the wheel. > the task was to model a drug that underwent 100% hepatic clearance. One > would not have [or want] PRE-DEFINED formulas to relate covariates and > clearance, and would start from scratch to identify significant covariate-CL > relationships. It seems you have not read the earlier portion of this thread in which I specifically pointed out the existence of a "pre-defined" allometric model which uses weight as the covariate to predict clearance such as hepatic clearance. Once again I prefer to rely on biology to help me understand rather than simply describe. -- Nick Holford, Dept Pharmacology & Clinical Pharmacology University of Auckland, 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