PharmPK Discussion - BE Study - AUC ratio

• On 26 Mar 2011 at 09:21:23, Wichittra Tassaneeyakul (wichittra.tassaneeyakul.at.gmail.com) sent the message
  

  
  Dear All,
  
  I have some questions that I would like your suugestion. What should we  do if we have
  conducted a BE study of a drug and found out that the  ratio of AUC0-t/AUC0-inf in 25-30%
  of subject are lower than 80%.
  
  Wichittra
  
  

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• On 26 Mar 2011 at 06:04:13, Aziz Karim (azia_karim.-at-.yahoo.com) sent the message
  

  
  This phenomenon could arise due to:
   1) The drug does not exhibit time-independent kinetics on multiple  dosing. Since in your
  case AUC (0-tau)ss/AUC (0-inf)sd is about 60%  there could be some auto-induction on
  mutiple dosing, example number of  anticonvulsant drugs.
   2) There is a concentration dependent protein binding. That is as the  plasma
  concentrations are increased on mutiple dosing, there is more of  free fraction produced
  which in turn is cleared. Here, the AUC ratio of  the total drug is less than one but of
  the unbound drug is approximately  one.See PK of naproxene or oxaprozin for example.
  
   Hope this helps.
   Aziz Karim
  
  

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