Re: metabolite modelling

From: "Stephen Duffull" <sduffull@fs1.pa.man.ac.uk> Subject: Re: metabolite modelling Date: Thu, 9 Dec 1999 15:20:59 -0000 Dick Wixley wrote: > I am trying to simultaneously model parent compound and metabolite. Oral > dosing - a 2-compartment model describes the parent compound well. > I have used the following code. It converged but took a long time but I was > not impressed with the results. ... ... > K24 =THETA(4)*EXP((ETA(4))) > K20 =THETA(6)*EXP((ETA(6))) > V2 =THETA(7)*EXP((ETA(7))) > V4 =THETA(8)*EXP((ETA(8))) All else being equal I think you have a structurally unidentifiable model. You are attempting to estimate K20 and K24. I believe that unless you have data on other fate of your drug (ie renal data or other metabolite) or you have data on administration of metabolite alone (in order to estimate V4) or you have prior data on the fraction of drug that meets the fate via K24 ... then "K24/V4" is globally identifiable but each parameter alone is not. Without additional data you have two choices: 1) set K20=0 (ie all drug is converted to metabolite) then K24 and V4 would both then be individually globally identifiable; or 2) fix V4=V2 then you would be ok. I hope this helps. Regards Steve ===================== Stephen Duffull School of Pharmacy University of Manchester Manchester, M13 9PL, UK Ph +44 161 275 2355 Fax +44 161 275 2396