Re: metabolite modeling
Date: Fri, 17 Dec 1999 09:41:37 -0800
From: Lewis B Sheiner <lewis@c255.ucsf.edu>
Subject: Re: metabolite modeling
Just so!
Thanks for such a clear and succinct statement.
LBS.
"Jean-Xavier.Mazoit@kb.u-psud.fr" wrote:
>
> Dear all,
> I followed with interest the debate about metabolite and identifiability of
> parameters (I am currently fitting morphine and glucuronide data using a
> similar model). Indeed, it is evident that the model presented by Dick is
> not fully identifiable. However, I am slightly astonished by all the
> discussions and arguments presented:
> In fact, the problem relates only to the difference between intensive and
> extensive variables. Rates are rates and concentrations are amounts
> divided by volumes. The linearity of the system and the principle of
> superposition tell us that concentration is proportional to the dose and
> inversely proportional to the volume. It is impossible to calculate
> volumes from concentrations without knowing the dose (for metabolites, the
> faction of the dose metabolised by the system). In other words, in a
> simple one compartment model, it is impossible to estimate the volume if
> 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. Also, it seems that there is a
> frequent confusion between identifiability which as an intrinsic property
> 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.
>
> Jean Xavier Mazoit MD, PhD
> Laboratoire d'Anesthésie
> Université Paris-Sud
> Faculté de Médecine du Kremlin-Bicêtre
> F-94276 Bicêtre France
> Tel. (33) (0)1 49 59 67 35-37
> (33) (0)1 45 21 34 41 (Hopital)
> Fax (33) (0)1 45 21 28 75
> e-mail Jean-Xavier.Mazoit@kb.u-psud.fr
--
Lewis B Sheiner Professor, Lab. Med., Biopharmaceut. Sci, Med.
Box 0626 - UCSF 415-476-1965 (voice)
San Francisco, CA 415-476-2796 (fax)
94143 lewis@c255.ucsf.edu