PharmPK Discussion - PK analysis after portal vein collection

• On 25 Jul 2006 at 23:09:31, "Tarra Fuchs" (tt1_chemistry.at.hotmail.com) sent the message
  

  
  The following message was posted to: PharmPK
  
  Recently we ran a prodrug PO PK in rats with portal vein cannulation.
  The orginal point of the experiment was to simply see if any intact
  prodrug made it to the portal vein (there is none detected and yes,
  we used esterase inhibitors in our collections).
  
  We collected several time points over several hours.  It is
  interesting to me that even at time points past the known absorption
  phase of the parent drug, concentrations in the portal vein are quite
  a bit higher than in systemic circulation.  May be this can be
  attributed to recirculation followed by more liver metabolism.
  
  At the risk of asking a very basic question,  I am wondering if the
  portal vein is truely considered part of the systemic circulatory
  system or can it serve as a eddy/trap of sorts where drug can
  concentrate momentarily after absorption (reabsorption).
  
  If it is not right to consider the portal vein as part of the
  systemic circulation, is there a volume correction I should use to
  correct my calculated concentrations? It seems they could be
  artifically high.
  
  Does anyone know the volume in the portal vein of a rat comapred to
  total volume or a reference with this type of information?
  
  Thanks,
  TFK
  
  

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• On 26 Jul 2006 at 09:58:52, David Stepensky (david.stepensky.-at-.yale.edu) sent the message
  

  
  The following message was posted to: PharmPK
  
  Dear Tarra,
  
  orally administered drug can undergo a variety of PK (or/and PD)
  events following its absorption and until reaching the 'true'
  systemic circulation in the 'peripheral' tissues (i.e., during its
  way through the GI wall, portal circulation, and liver). Due to this,
  the time course of the drug & metabolites concentrations in the
  portal vein may be different from that in the 'peripheral' tissues.
  
  In your case, portal vein concentrations of the active drug could be
  higher than the systemic concentrations, for example, if metabolism
  of the prodrug to the active drug takes place in the GI lumen or
  wall, or in case of the enterohepatic circulation.
  
  Regards,
  
  David.
  
  David Stepensky
  HHMI Postdoc Associate
  Department of Immunobiology
  Yale University School of Medicine
  
  

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