From: varun goel varun_goel_9@yahoo.com
Subject: [NMusers] Simulation of Steady state concentration of Phenytoin
Date: Sun, 11 Jun 2006 14:14:39 -0700 (PDT)

Dear All,
I am trying to simulate steady state concentrations of phenytoin with
TDM in Nonmem. I  am simulating Vmax  and  Km  values  according  to 
published  literature. However I get in trouble while adjusting for dose.
As I desire the concentrations levels to lie in the window of 5-25 ug/mL.
I manually  have to change the dosing records for concetrations that  are
low or go very high (sometimes enormous concentrations when Vmax is lower
than dose). 
I am looking for suggestions regarding making it more  automated in Nonmem.
Any references or suggestions on this matter is highly appreciated.

Thanks

Varun Goel
Graduate Student
Experimantal and Clinical Pharmacology
University of Minnesota, Minneapolis, MN
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From: Mark Sale - Next Level Solutions mark@nextlevelsolns.com
Subject: RE: [NMusers] Simulation of Steady state concentration of Phenytoin
Date: Sun, 11 Jun 2006 15:04:12 -0700

Varun,

One option is to change the bioavailability.  Set it to 1 initially, with a dose
of 1000, then if you want to give 1100, just change bioavailability to 1.1, so
you don't have to recreate the data set.  I'm not aware of canned solution to
doing this, I don't think that Trial Simulator will (but those who know it better
may correct me).  Personally, I'd write an Excel macro that would run NONMEM, read
the results, then recreate a data set with a different dose.  People more sophistocated
than I am would probably do it in S plus.


Mark Sale MD
Next Level Solutions, LLC
www.NextLevelSolns.com

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From: "Bill Bachman" bachmanw@comcast.net
Subject: RE: [NMusers] Simulation of Steady state concentration of Phenytoin
Date: Fri, 23 Jun 2006 08:49:15 -0400

Trial Simulator will do this (it has a nice dose adjustment feature that allows you to readily
do randomized concentration (response) controlled clinical trials).  If you want to “roll-your-own”,
another language that works well (in addition to Excel macros or S-Plus or R) is Perl.
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