PharmPK Discussion - Extraction Ratio

• On 10 Jan 2013 at 17:41:00, Xinting Wang (wxinting1986.-at-.gmail.com) sent the message
  

  
  Dear all,
  
  Can anybody please help explain the following equation to calculate ER
  (extraction ratio)? I saw that many paper calculating CLorgan used this
  equation but none of them provided explanation to it.
  
  ER =fu*CLint/(Qorgan + fu*CLint)
  
  Where,
  ER= Extraction Ratio
  CLint= intrinsic clearance
  Qorgan=organ blood flow
  fu=unbound fraction of the compound
  
  Thanks and Regards
  
  Xinting
  
  [See also http://www.boomer.org/c/p4/c17/c1704.html
  - db]
  
  

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• On 10 Jan 2013 at 11:07:04, Chris (chris_kemper.-a-.pharmanavigatorsllc.com) sent the message
  

  
  The following message was posted to: PharmPK
  
  Xinting:
  
  That equation is derived from the basic relationship
  
  ER = (Cin-Cout)/Cin,
  
  Where Cin and Cout are the concentrations in and out of the clearing
  organ.
  There are several intermediate equations in the derivation that can be
  found
  in many PK texts, including Pharmacokinetic and Pharmacodynamic Data
  Analysis by Gabrielson and Weiner (Apotekarsocietetan 2001)
  
  Chris
  
  Christopher J. Kemper, Ph.D.
  Pharma Navigators, LLC
  DMPK/Bioanalytical Consulting
  Alliance Management/Business Analysis
  
  

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• On 10 Jan 2013 at 16:40:00, William Wolowich (wwolowic.-at-.nova.edu) sent the message
  

  
  The following message was posted to: PharmPK
  
  Xinting: Do the math:
  
  Er,organ = CLorgan / Qorgan (for the liver is Er = CLh/LBF)
  Er = (Qorgan*fu*CLint/ (Qorgan + fu*CLint)) / Qorgan
  Er = fu*CLint / (Qorgan + fu*CLint)
  
  William R. Wolowich, Pharm.D., R.Ph.
  College of Pharmacy
  Nova Southeastern University
  wwolowic.-a-.nova.edu
  
  [For the well-stirred model, see also http://www.boomer.org/c/p4/ja/Fig1702/Fig1702.html
  - db]
  

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• On 15 Jan 2013 at 10:51:08, "J.H.Proost" (j.h.proost.-at-.rug.nl) sent the message
  

  
  Dear Zinting,
  
  In addition to the useful link provided by David Bourne, the following
  may be helpful to understand the relationship describing the extraction
  ratio.
  
  1) total hepatic blood flow (QH),
  2) fraction unbound (fU) or the extent of drug binding to blood
  constituents.
  3) free intrinsic clearance (CLint) or the rate-limiting step in drug
  uptake from blood, intracellular transport, metabolism.
  
  Consider a drug molecule in the hepatic sinusoids: two things may
  happen:
  
  a) the molecule escapes hepatic extraction: this chance is proportional
  to Q_H (and the drug concentration in the blood);
  b) the molecule enters a hepatocyte and is metabolized; this chance is
  proportional to fu (only free drug enters the liver) and proportional to
  CLint (and the drug concentration in the blood).
  
  So, the chance that a molecule is extracted from the blood, is the
  chance of b) divided by the som of a) and b), or (after dividing both by
  the blood concentration):
  
  E_H = (fu * CLint) / (Q_H  +  fu * CLint).
  
  This is a very simplistic derivation, and should not be regarded as a
  formal proof, but for understand the relationship between the three
  factors (Q_H, fu, CLint) and the extraction ratio it is quite useful in
  my teaching experience.
  
  best regards,
  
  Hans Proost
  
  Johannes H. Proost
  Dept. of Pharmacokinetics, Toxicology and Targeting
  University Centre for Pharmacy
  Antonius Deusinglaan 1
  9713 AV Groningen, The Netherlands
  
  

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