Simulation of Steady state concentration of Phenytoin

3 messages 3 people Latest: Jun 23, 2006
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
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
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. _______________________________________________________