From:Prof LJ Van Obbergh
Subject:[NMusers] Bioavailability and P-Gp
Date:Tue, 28 Jan 2003 

 Dear friends,

 we would like to determine the bioavalability of a drug transported through
 the intestinal barrier by P-Gp before and after blocking of P-Gp in children.
 by comparaison of the AUC obtained with an iv and and oral dose.
 Would it be possible to conduct this study with a population approach as we
 would like to limit the amount of blood samples.

 If yes, how would you write the control stream for NONMEM describing this

 thank you in advance for your help.

 Prof LJ Van Obbergh
 University Clinics St Luc
 Catholic University of Louvain
 10 1821 av Hippocrate
 1200 Brussels
 Tf 3227641821
 Fax 3227643699

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:

I hope this helps,


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

Van Obbergh wrote: