PharmPK Discussion - Clearance greater than blood flow

• On 23 Jul 2013 at 08:16:39, MJ sent the message
  

  
  Dear all,
  When I read some textbook on PK, there are some views that really confusing me.  Would you please
  feel free give your comments to specify them?
  
  1)       "Plasma clearance if often found to be greater than the blood flow rate of the eliminating
  organ(s) such as the liver, which is the upper limit of the organ clearance.  This may indicate the
  drug partitions more to red blood cells than to plasma, and drug molecules bound to red blood cells
  are also available for extraction by the organ."
  
  Any comments on these views will be highly appreciated.
  
  Thanks in advance,
  MJ
  
  

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• On 23 Jul 2013 at 08:59:36, Hans Proost sent the message
  

  
  Dear MJ,
  
  First, assume that the liver is the only eliminating organ. The amount of drug eliminated per unit
  of time can never be larger than the amount of drug entering the liver per unit of time. This amount
  of drug eliminated per unit of time, or elimination rate, is usually denote as a differential
  quotient dA/dt, where A is the amount in the body. Now we define plasma clearance (CL) and blood
  clearance (CLb)
  
  dA/dt = CL * C = CLb * Cb
  
  where C is the plasma concentration entering the liver (i.e. in the system) and Cb is the
  corresponding blood concentration.
  CLb cannot be larger than the liver blood flow Qh, as a result of the above restriction. This can be
  written as
  
  CLb = Eh * Qh
  
  where Eh is the hepatic extraction ratio (between 0 and 1)
  
  For drugs partitioning more to red blood cells than to plasma, the blood concentration Cb exceeds
  the plasma concentration C. To maintain the above equation (which is true by definition), CL can be
  written:
  
  CL =  CLb * Cb / C = Eh * Qh * Cb / C
  
  CL will be higher than Qh if the product of the extraction ratio Eh and the blood/plasma ratio Cb/C
  exceeds 1. This will occur only if Eh is high (close to 1), and the blood/plasma ratio Cb/C (well
  above 1).
  
  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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