2006D-0344
  

  
 Guidance for Industry on Drug Interaction Studies--Study Design, Data Analysis, and Implications for Dosing and Labeling

  


  

  

  


  

  


  

  


  

  
FDA Comment Number : 
  

  
EC9
  



  

  
Submitter : 
  

  
Dr. Andrew Parkinson
  

  
Date & Time: 
  

  
11/13/2006 11:11:06
  



  

  
Organization : 
  

  
XenoTech, LLC
  



  

  
Category : 
  

  
Drug Industry
  



  

  
Issue Areas/Comments 
  


  

  


  

  
GENERAL
  


  

  



  

  
GENERAL
  


  

  



  

  
 Although gemfibrozil is an effective CYP2C8 inhibitor in vivo, gemfibrozil itself is not an effective inhibitor of CYP2C8 in human liver microsomal incubations in vitro.  However, gemfibrozil glucuronide, a major metabolite of gemfibrozil, is a potent, mechanism-based inhibitor of CYP2C8 (Ogilvie BW, Zhang D, Li W, Rodrigues AD, Gipson AE, Holsapple J, Toren P and Parkinson A: Glucuronidation converts gemfibrozil to a potent, metabolism-dependent inhibitor of CYP2C8: implications for drug-drug interactions. Drug Metab Dispos 34:191-197, 2006).