Re: metabolite modeling

From: "Stephen Duffull" <sduffull@fs1.pa.man.ac.uk> Subject: Re: metabolite modeling Date: Thu, 9 Dec 1999 17:12:32 -0000 Matthew I'm do not agree on this point. > parameters should be unique. My reasoning is as follows: All parameters > k12,k23,k32,V1,k20* (k20*=k20+k24) are identifiable in fitting the parent > alone with the two compartment model. If one adds in the metabolite, then > k24 can be estimated by the conversion portion of the metabolite data so > that the parameters k24,V4,k40 should all be identifiable. As the model was described V4 is not identifiable since the amount of drug that gets converted to metabolite is not known. An analogous example would be a 1 compartment oral absorption model where V is not identifiable but V/F is - but if F is known a priori then V is identifiable. K24 includes Fm (fraction of drug that goes to the metabolite) implicitly. If Fm is known (as you suggest when you say "conversion portion") then I agree V4 and K24 become identifiable. Setting Fm to one (ie (1-Fm)*K20 = 0) solves this problem although may not be correct, any value for Fm could be chosen - and some prior knowledge is likely to be known. To conclude if either of Fm or V4 are known then K24 and the other can be computed but without additional information the choice is to fix Fm or V4. It should be considered that non-linear regression programs often give parameter estimates for unidentifiable models and tell the user that all was well therefore care must be taken to ensure all parameters are identifiable. Regards Steve ===================== Stephen Duffull School of Pharmacy University of Manchester Manchester, M13 9PL, UK Ph +44 161 275 2355 Fax +44 161 275 2396