PharmPK Discussion - Hepatic blood flow in each species

• On 15 Mar 2010 at 09:30:24, wangjian (wj801126.at.hotmail.com) sent the message
  

  
  Hi, All:
      I'm wondering if there are uniform values of hepatic blood flow for mouse, rat, dog, monkey and human, which are used to classify one compound as high, medium or low hepatic extraction. I have seen many different values used by different labs, different companies such as for rats, someone use 70 mL/min/kg, but someone use 55.2 mL/min/kg. And for mouse, someone use 90 mL/min/kg, but someone use 110 mL/min/kg. Which one is right? How can we use these hepatic blood flow to judge a compound's clearance? Thanks!
  
  Jian
  
  

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• On 15 Mar 2010 at 15:29:14, "Stefano Porzio" (porzio.at.bioindustrypark.it) sent the message
  

  
  The following message was posted to: PharmPK
  
  Dear Jian,
  to classify hepatic clearance, due to different blood flow in different species,  it's often suggested to use a "fraction of blood flow" (i.e. <20%, < 50%, <100%  or > 100%).
  
  Kind regards
  Stefano
  
  

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• On 15 Mar 2010 at 14:43:08, "Simon Clark" (SJClark.-a-.pharm.co.uk) sent the message
  

  
  The following message was posted to: PharmPK
  
  Dear Jian,
  
  Usually industry practices involve established values from literature and use these as the standard parameter which they compare Cl(p) against, as a relative degree of plasma clearance within species for the compound. For example stratified proportions of respective hepatic blood flow could be placed it to ranges as follows:
  
  Cl(p)        Q (HBF)
  LOW -      <1/3
  MEDIUM -    0.3-0.7
  HIGH-       >0.7
  VERY HIGH   Greater than Hepatic Blood Flow
  
  Sorry my PBPK knowledge is basic
  
  In general...
  
  Cl = QE
  
  Where E is the extraction ratio of the compound by the liver or E= C blood in - C blood out
                                                                     ------------------------
                                                                           C blood in
  
  But dont forget....
  
  Cl(plasma) = Cl (metabolic) + Cl (renal)
  
  And some well qualified (Pharm.Res 10 1093-1095) HBF values (ml/min/kg)
  
  Mouse (20-25g)       90
  Rat                  85
  Rabbit (2.5 - 3kg)   71
  Dog (10-12Kg)        31
  Monkey (4-5kg)       44
  Human (70kg)         21
  
  Really hope this helps, although I'm sure we'll be told otherwise : )
  
  Simon C
  
  

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• On 18 Mar 2010 at 09:29:18, "Tausif Ahmed (Dr.)" (tausif.a.at.saiadvantium.com) sent the message
  

  
  The following message was posted to: PharmPK
  
  Hi Jian,
  
  Thanks for sharing the values in detail. I just had doubt on the HBF value of rat. It is 55 ml/min/kg and not 85 ml/min/kg. Majority of the papers mention it as 55 ml/min/kg.
  
  Ref :  SJ Tschida et al. (1995)  Med. Clin. N. Amer. 79: 895-917
            DD Breimer. (1987)  Pharm. Weekbl. Sci. 9: 79-84
  Thanks
  
  Tausif Ahmed, Ph.D.
  Principal Scientist, DMPK
  Sai Advantium Pharma Ltd., Pune
  
  

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• On 18 Mar 2010 at 11:12:21, Clerk Maxwell (clerkmaxwell.aaa.hotmail.com) sent the message
  

  
  Neglect the clerkmaxwell name, as I am Harold Boxenbaum:
   While the reference below gives good values, I have conducted an extensive literature review, and I have come up with what I believe is the best value for HBF in humans, viz., 25 mL/min/kg.  Anyone can contact me for my calculation:
   Harold Boxenbaum, Ph.D.
  Pharmacokinetic Consultant
  Arishel Inc.
  14621 Settlers Landing Way
  North Potomac, MD 20878-4305
  
  

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