Bioavailability and P-Gp

From:Scott VanWart Subject:[NMusers] Bioavailability and P-Gp Date:Tue, 28 Jan 2003 18:34:05 -0500 Dear Sir, I would think that what you are describing can be accomplished with the population approach provided that your sampling scheme is designed appropriately to enable you to characterize the pharmacokinetics of the drug. Selection of sampling times will depend upon the pharmacokinetic properties of the drug you are working with. I assume you would be conducting a three-way crossover: (1) iv, (2) oral drug, and (3) oral drug + a potent P-Gp inhibitor drug. One approach could be to simultaneously fit the iv data with the oral data and allow for differences in F for the oral drug when in the presence of the P-Gp inhibitor. Before anyone can provide you assistance with modeling your data using NONMEM, you must have an idea of the mathematical/compartmental model you wish to use to describe the data. If the pharmacokinetics of the drug you are working with have already been studied in some capacity, this will provide a very important basis for any future work you do. Unfortunately, there is not a library model that can be used for simultaneous fitting, however you have the ability to specify the appropriate system of differential equations within the NONMEM control stream. From time to time, members of this group have been kind enough to submit sample coding and descriptions for some of the work they have performed. A good starting point would be to search the NONMEM user's archive: http://www.cognigencorp.com/nonmem/nm/ I hope this helps, Scott ------------------------------- Scott Van Wart Population PK/PD Scientist Cognigen Corporation 395 Youngs Road Williamsville, NY 14221 Tel. (716) 633-3463 Ext 241 Fax. (716) 633-7404 email: scott.vanwart@cognigencorp.com Web: www.cognigencorp.com Van Obbergh wrote: _________________________________________