RE: Scaling for pediatric study planning
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
Quoted reply history
-----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.