Re: metabolite modeling

Date: Fri, 17 Dec 1999 21:30:21 +1300 From: Nick Holford <n.holford@auckland.ac.nz> Subject: Re: metabolite modeling "Jean-Xavier.Mazoit@kb.u-psud.fr" wrote: > the dose is unknown. On another hand, it is always possible to estimate > half-life (or rate constant, or time constant) which is a basic parameter, > contrary to Nick Holford's opinion. Its all a matter of perspective. If you think only in terms of amount then half-life does seem to be the basic parameter but its a rather weak conceptual framework because to connect half-life to a real drug elimination process e.g. metabolism or renal excretion then I find it hard to imagine a process that is driven by amount rather than by concentration. From the perspective of concentration I find it is much easier to imagine concentration driven physical processes. Given the concentration viewpoint then volume and clearance become the natural basic parameters and half-life is clearly a derived parameter. I can readily propose physical mechanisms that can independently change either clearance of volume but there are no physical mechanisms which control half-life independently of either clearance or volume. Being able to estimate a parameter is not a sufficient criterion for considering it a primary or basic parameter. We can readily compute AUC but that does not make it a basic parameter. AUC and dose can be used to estimate CL which is the basic parameter. > of the system and sensitivity. With that respect, I think that most > considerations presented in David Bourne's course on identifiability deal > with sensitivity rather than with identifiability. I agree with you here. I think it is not a good idea to mix up identifiability with sensitivity sometimes called a posteriori identifiability. Sensitivity is a continuous reflection of the experimental design points whereas identifiability is a binary property of a parameter given a specific design. -- 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.html