metabolite modeling

Date: Fri, 17 Dec 1999 09:01:56 +0100 From: "Jean-Xavier.Mazoit@kb.u-psud.fr" <Jean-Xavier.Mazoit@kb.u-psud.fr> Subject: metabolite modeling 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