PharmPK Discussion - Intrinsic clearance calculation with hepatocytes

• On 11 Aug 2011 at 22:48:42, (Venkata.Vijaykumar.at.syngeneintl.com) sent the message
  

  
  Hi Everybody,
  
  Can anyone help me in calculating intrinsic clearance with hepatocytes.
  I would like to know the formula used for this purpose.
  
  Thanks and regards
  N.V.Vijay Kumar Mamidi
  
  Biology Research & Development (Bio-Analytical)
  Syngene International Ltd.
  Email: venkata.vijaykumar.-at-.syngeneintl.com
  
  

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• On 12 Aug 2011 at 20:39:15, shanti chowdary (santhi.au2010.at.gmail.com) sent the message
  

  
  Hi vijay,
  
  The formula for intrinsic hepatic clearance is Rate of elimination by
  liver/plasma drug concentration.
  
  Hope this helps you.
  
  Best Regards,
  Shanti.
  
  

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• On 16 Aug 2011 at 08:24:36, Jitendar Reddy (sjeetu2u.aaa.gmail.com) sent the message
  

  
  Hi Vijay,
  
  I understand that you will be planning or did in-vitro experiments with Hepatocytes.
  
  1. You will get a value that might be for a million cells (e^6) i.e = uL/min/e^6
  
  2. You multiply that value with Hepatocellularity of respective species (per gram liver),
  then normalise for the Kg body weight, it will be uL/min/kg. Please refer your company
  document for Hepatocellularity values, coz each company has its own standard values.
  
  This will give you the Intrinsic CL with hepatocytes
  
  I hope i answered your query
  
  Cheers,
  Jitendar Reddy
  DMPK, AstraZeneca, Bangalore, India
  

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• On 16 Aug 2011 at 21:01:10, Masoud Jamei (masoud.jamei.-at-.gmail.com) sent the message
  

  
  Hi Vijay
  
  For a complete set of calculations you can see the following paper, in
  particular section "Method One--bottom-up calculation of CLint".
  
  Cubitt HE, Yeo KR, Howgate EM, Rostami-Hodjegan A and Barter ZE (2011)
  Sources of interindividual variability in IVIVE of clearance: an
  investigation into the prediction of benzodiazepine clearance using a
  mechanistic population-based pharmacokinetic model. Xenobiotica
  41:623-638.
  
  Regards
  Masoud
  
  

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