Re: Scaling for pediatric study planning

Title: Paul R Dear Leonid: Regarding d): I would not expect to need to scale the KM at all unless the affinity of the substrate (drug) is known to be different between species. Size alone would not be expected to affect the KM of elimination. It could clearly affect the KM of a passive or active gut absorption process due to the surface area of the intestine. my $0.02 Paul Leonid Gibiansky wrote: 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.