PharmPK Discussion - Plasma versus Serum Protein Binding

• On 9 Jan 2012 at 13:20:29, David Benziger (David.Benziger.-at-.cubist.com) sent the message
  

  
  We have a compound that exits about 20% protein binding in human plasma
  and about 15% in human serum.
  
  Have others seen similar differences between plasma and serum?  Any
  thoughts on cause of difference?
  
  Which value would be more meaningful if you want to model "free drug"
  concentrations?
  
  Thanks - Dave
  
  

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• On 9 Jan 2012 at 14:16:46, Stanley Cotler (msgcot2.-at-.optimum.net) sent the message
  

  
  The following message was posted to: PharmPK
  
  There is possible binding to alpha-glcoprotein.
                                    Stanley Cotler
  
  

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• On 9 Jan 2012 at 14:59:26, (Ttarnowski1.aaa.aol.com) sent the message
  

  
  Dear Dave,
  Regarding why a compound may exhibit 20% protein binding in human plasma
  and about 15% in human serum, a few possibilities (or combinations of
  one or more of these):
  1.  The compound may bind to some extent to either the proteins involved
  in clotting or to the clots, and are therefore partially removed when
  the proteins/clots are removed to form serum.
  2.  Anticoagulant in the plasma may somehow promote binding to the
  plasma proteins, (or to a plasma-protein-antigoagulant complex) or
  interfere in some way with determination of the compound.
  3.  There may be a volume differential between plasma and serum from the
  same blood sample.
  
  I expect others on this newsgroup may have other possibilities.
  
  Tom
  
  Thomas L. Tarnowski, Ph.D.
  Bioanalytics and CMC
  ttarnowski1.at.aol.com
  
  

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• On 9 Jan 2012 at 16:10:38, Peter W Mullen (pmullen.aaa.kemic.com) sent the message
  

  
  Hi Dave,
  
  I would think it's quite possible that there's no real difference (as
  opposed to analytical/procedural variation) between 20% (plasma) and 15%
  (serum) protein binding?
  
  Some questions, out of curiosity:
      How was the extent of binding determined?
      Number of replicates?
      What anticoagulant was used for obtaining plasma?
  
  "Happy New Year!"
  
  Regards,
  Peter
  
  Peter W. Mullen, PhD, FCSFS
  KEMIC BIORESEARCH (www.kemic.com)
  Kentville
  Nova Scotia, B4N 4H8
  Canada
  
  

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• On 10 Jan 2012 at 10:11:18, Ravi Bhatia (pharmarkb.-at-.gmail.com) sent the message
  

  
  The following message was posted to: PharmPK
  
  Dear Dave
  
  You can check the pH difference between serum and plasma for this
  small difference in binding.
  Reference: Ohehlma T. et. al., "Variations in Protein Binding of Drugs
  in Plasma and Serum" CLIN. CHEM. 35/8, 1722-1725 (1989)
  
  Kind Regards
  Ravi
  
  

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• On 10 Jan 2012 at 08:00:53, (dale.sharp.-a-.boehringer-ingelheim.com) sent the message
  

  
  The following message was posted to: PharmPK
  
  Dave,
  
  I've been reading this thread and there are all sorts of technical
  ideas, but
  in my opinion nobody is considering the big picture; that is, the
  difference
  between 80% free and 85% free is almost certainly negligible unless the
  PK
  variability of the drug is much lower than anything I know about.  All
  these
  fixes are purely academic.
  
  Dale
  
  

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• On 10 Jan 2012 at 14:33:36, David Benziger (David.Benziger.at.cubist.com) sent the message
  

  
  The following message was posted to: PharmPK
  
  Peter,
  
  14-C labeled, 0.5, 5.0 and 50 ug/mL, ultrafiltration ("Centrifree
  tubes"),  1 ml plasma(Na heparin)/serum centrifuged to get 20% or less volume (15
  min) at 3000 rpm at 37 C,3 replicates at each of three concentrations (+/-SE)
  
                         0.5           5.0              50
  
  Plasma 16.27 - 20.84% (20.84+/-1.65, 16.27+/-1.61 and 19.67+/-0.19)
  Serum  14.57 - 16.76% (14.63+/-2.05, 16.76+/-0.36 and 14.57+/-0.34)
  
  

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Copyright 1995-2011 David W. A. Bourne (david@boomer.org)