RE: Scaling for pediatric study planning

-----Original Message----- From: [EMAIL PROTECTED] [mailto:[EMAIL PROTECTED] On Behalf Of Leonid Gibiansky Sent: Friday, September 19, 2008 12:07 PM To: Joseph Standing Cc: [EMAIL PROTECTED]; [email protected] Subject: Re: [NMusers] Scaling for pediatric study planning Joe, We could be talking about different VM definitions I am thinking about the model DADT(1)= -A(1)*VM/(KM+C1) - K10*A(1) If we believe that the ratio of linear to nonlinear elimination should not depend on WT (?), then k10 and VM should be scaled similarly ~ WT**(-0.25) If we present the same equation as DADT(1)= -C1*VM'/(KM+C1) - K10*A(1) then DADT(1)= -A(1)*(VM'/V1)/(KM+C1) - K10*A(1) VM' is indeed should be scaled as WT**0.75 (thus leading to VM scaled as WT**(-0.25). Leonid -------------------------------------- Leonid Gibiansky, Ph.D. President, QuantPharm LLC web: www.quantpharm.com e-mail: LGibiansky at quantpharm.com tel: (301) 767 5566 Joseph Standing wrote: > Here's my philosophy: > > c) VM scales to wt**0.75 as it is a measure of enzyme concentration and > liver volume relative to body size goes wt**0.75 (Johnson TN et al. 2005) - > any age-related differences to this are due to developmental factors. > d) KM - don't scale it, it is a measure of enzyme affinity and shouldn't > change with size, differences are due to polymorphisms. > BW, > > Joe > > > -----Original Message----- > From: [EMAIL PROTECTED] [mailto:[EMAIL PROTECTED] On > Behalf Of Leonid Gibiansky > Sent: den 19 september 2008 17:21 > To: [EMAIL PROTECTED] > Cc: [email protected] > Subject: Re: [NMusers] Scaling for pediatric study planning > > Just to add: > > c) how do we allometrically scale a VM rate constant of the > Michaelis-Menten elimination model: > > C1=A(1)/V1 > DADT(1)= ... -A(1)*VM/(KM+C1) > > d) do we need to allometrically scale a KM constant of the > Michaelis-Menten elimination model ? > > any experience with these quantities (for example, if they were > estimated, what were the estimates, with the precision)? > > > My suggestion would be NOT to scale a), b) and d), and scale VM as the > rate constant (~ WT**(-0.25)) but I do not have "rock-solid" data to > support those suggestions. > > Leonid > -------------------------------------- > Leonid Gibiansky, Ph.D. > President, QuantPharm LLC > web: www.quantpharm.com > e-mail: LGibiansky at quantpharm.com > tel: (301) 767 5566 > > > > > [EMAIL PROTECTED] wrote: >> Dear NM_Users, >> >> we have all been good students and listened to Nick when he told us >> again and again the rock-solid truths of allometry: >> >> Volume: *(WT/70) >> >> CL: *(WT/70)**0.75 >> >> any rate constant related to distribution or elimination: > *(WT/70)**(-0.25) >> Here my questions: >> a) how do we allometrically scale a first-order rate constant of >> absorption after oral dosing? >> >> b) how do we allometrically scale a first-order rate constant of >> absorption from a subcutaneous injection site? >> >> Thank you for your thoughts, >> >> Joachim >> >> __________________________________________ >> Joachim GREVEL, Ph.D. >> MERCK SERONO International S.A. >> Exploratory Medicine >> 1202 Geneva >> Tel: +41.22.414.4751 >> Fax: +41.22.414.3059 >> Email: [EMAIL PROTECTED] >> >> ------------------------------------------------------------------------ >> >> This message and any attachment are confidential, may be privileged or >> otherwise protected from disclosure and are intended only for use by the >> addressee(s) named herein. If you are not the intended recipient, you >> must not copy this message or attachment or disclose the contents to any >> other person. If you have received this transmission in error, please >> notify the sender immediately and delete the message and any attachment >> from your system.