NONMEM Users Network Archive

Hosted by Cognigen

RE: Scaling for pediatric study planning

From: Joseph Standing <joseph.standing>
Date: Fri, 19 Sep 2008 17:51:39 +0200

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: owner-nmusers
Behalf Of Leonid Gibiansky
Sent: den 19 september 2008 17:21
To: Joachim.Grevel
Cc: nmusers
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




Joachim.Grevel
>
> 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: joachim.grevel
>
> ------------------------------------------------------------------------
>
> 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. Merck Serono does not accept liability for any
> omissions or errors in this message which may arise as a result of
> E-Mail-transmission or for damages resulting from any unauthorized
> changes of the content of this message and any attachment thereto. If
> verification is required, please request a hard-copy version. Merck
> Serono does not guarantee that this message is free of viruses and does
> not accept liability for any damages caused by any virus transmitted
> therewith.
>
Received on Fri Sep 19 2008 - 11:51:39 EDT

The NONMEM Users Network is maintained by ICON plc. Requests to subscribe to the network should be sent to: nmusers-request@iconplc.com.

Once subscribed, you may contribute to the discussion by emailing: nmusers@globomaxnm.com.