Antwort: Re: change from mass to molar units

Nick, oh, sorry about that, that was a typo. I have mg and µg/L and µmol and nmol/L, so I'm afraid that's not the reason. I have a combined error model. However, although I needed the additive error to get the model to run, I fixed it to a very small value (0.0001). But to make sure I just adjusted this value too, with the same result. Just to get this clear for me...in theory the parameters should be the same, shouldn't they? So if this keeps on happening, what else can I do? I was thinking about recalculating the metabolite concentrations by dividing them with their molar mass and then multiplying with the molar mass of the parent. Would this be a reasonable approach, just to pretend that the metabolite is parent by using this calculation? Would the metabolite parameters still be correct then? Thanks for your help. Nele _________________________ Nele Plock Bayer Schering Pharma AG GPD/Pharmacokinetics Metabolism & Bioanalysis D- 13342 Berlin Phone : +49-30-468 15146 Fax: +49-30-468 95146 [EMAIL PROTECTED] Nick Holford <[EMAIL PROTECTED]> 08.03.2007 15:10 An [EMAIL PROTECTED] Kopie [email protected] Thema Re: [NMusers] change from mass to molar units Nele, Two suggestions: 1. You have mass units of mg and mg/L but molar units of nmol/1000 and nmol/L. So the ratio of AMT to DV is different by a factor of 1000 2. If you have an additive error model then the scale of the residual error model parameter will need to change. Best wishes, Nick [EMAIL PROTECTED] wrote: > > Dear all, > > I have fitted a simple two-compartment model with linear elimination to > some compound data (ADVAN4 TRANS4). Everything worked well. Because I want > to extend this model to account for metabolite data as well, I now wanted > to change all data to molar units, i.e. I changed the AMT and DV column in > the same way. To my understanding, if I change both these columns, the > obtained parameters should end up being the same. However, when I use mg > and µg/mL the model runs just fine, whereas when I use µmol and nmol/L the > parameter estimates change completely and always run into some boundary. > Can anyone shed some light on why this happens? Is there any way to get > around this? Could I keep the mass units and do some changes in the > control stream when incorporating the metabolite data? Any help would be > highly appreciated. > > Best regards > Nele > > _________________________ > Nele Plock > Bayer Schering Pharma AG > GPD/Pharmacokinetics > Metabolism & Bioanalysis > D- 13342 Berlin > > Phone : +49-30-468 15146 > Fax: +49-30-468 95146 > [EMAIL PROTECTED] -- Nick Holford, Dept Pharmacology & Clinical Pharmacology University of Auckland, 85 Park Rd, Private Bag 92019, Auckland, New Zealand email:[EMAIL PROTECTED] tel:+64(9)373-7599x86730 fax:373-7556 http://www.health.auckland.ac.nz/pharmacology/staff/nholford/

Theoretically, the parameter estimates should be the same for the parent (if the input, e.g., oral, is exactly in the form of the parent), no matter you use the mass unit or the molar unit. However, for the metabolite, the parameter estimates should be different when different concentration units are used UNLESS the molecular weight of the metabolite happens to be the same as or very close to MW for the parent. Alan

Since theoretically rescaling should not matter, the problem is in details that can not be extracted from the description without seeing the data and control stream. Just as an experiment (and to check your data creation process) run the model with the data where AMT and DV are rescaled by a factor of, say 1.1. If you see the difference there, you probably made an error in the data creation script. If it runs OK (returns exactly the same parameter estimates), increase (or decrease) the rescaling factor until it break the solution. Let us know what happens, it may help to diagnose the problem. If the problem appear at some value of the rescaling factor, it may indicate rounding error or something similar. Try to use mcmol or nmol or anything in between to have concentration and dose of the same order of magnitude as in mg form. Another test: try to start with the solution as initial values. Yet another try: use simpler 1-compartment (ADVAN2) model for both sets of data to see whether the problem is universal or ADVAN-specific. If it is universal, it would point to the data creation error. Leonid [EMAIL PROTECTED] wrote: > Nick, > > oh, sorry about that, that was a typo. I have mg and µg/L and µmol and nmol/L, so I'm afraid that's not the reason. I have a combined error model. However, although I needed the additive error to get the model to run, I fixed it to a very small value (0.0001). But to make sure I just adjusted this value too, with the same result. Just to get this clear for me...in theory the parameters should be the same, shouldn't they? So if this keeps on happening, what else can I do? I was thinking about recalculating the metabolite concentrations by dividing them with their molar mass and then multiplying with the molar mass of the parent. Would this be a reasonable approach, just to pretend that the metabolite is parent by using this calculation? Would the metabolite parameters still be correct then? > > Thanks for your help. > Nele > _________________________ > Nele Plock > Bayer Schering Pharma AG > GPD/Pharmacokinetics > Metabolism & Bioanalysis > D- 13342 Berlin > > Phone : +49-30-468 15146 > Fax: +49-30-468 95146 > [EMAIL PROTECTED] > > Nick Holford <[EMAIL PROTECTED]> 08.03.2007 15:10 > > An > [EMAIL PROTECTED] > Kopie > [email protected] > Thema > Re: [NMusers] change from mass to molar units > > Nele, > > Two suggestions: > > 1. You have mass units of mg and mg/L but molar units of nmol/1000 and nmol/L. So the ratio of AMT to DV is different by a factor of 1000 > > 2. If you have an additive error model then the scale of the residual error model parameter will need to change. > > Best wishes, > > Nick > > [EMAIL PROTECTED] wrote: > > > Dear all, > > > > I have fitted a simple two-compartment model with linear elimination to > > > > some compound data (ADVAN4 TRANS4). Everything worked well. Because I > > want > > > to extend this model to account for metabolite data as well, I now > > wanted > > > to change all data to molar units, i.e. I changed the AMT and DV column > > in > > > the same way. To my understanding, if I change both these columns, the > > obtained parameters should end up being the same. However, when I use mg > > > > and µg/mL the model runs just fine, whereas when I use µmol and nmol/L > > the > > > parameter estimates change completely and always run into some boundary. > > Can anyone shed some light on why this happens? Is there any way to get > > around this? Could I keep the mass units and do some changes in the > > control stream when incorporating the metabolite data? Any help would be > > highly appreciated. > > > > Best regards > > Nele > > > > _________________________ > > Nele Plock > > Bayer Schering Pharma AG > > GPD/Pharmacokinetics > > Metabolism & Bioanalysis > > D- 13342 Berlin > > > > Phone : +49-30-468 15146 > > Fax: +49-30-468 95146 > > [EMAIL PROTECTED] > > -- > Nick Holford, Dept Pharmacology & Clinical Pharmacology > > University of Auckland, 85 Park Rd, Private Bag 92019, Auckland, New Zealand > > email:[EMAIL PROTECTED] tel:+64(9)373-7599x86730 fax:373-7556 > http://www.health.auckland.ac.nz/pharmacology/staff/nholford/

Nele, Consider adjusting the fixed small additive error (0.0001) by the molecular weight similar to the adjustments made to dose and plasma concentrations. Otherwise, everything else should work the same. Good Luck!! Steve