PharmPK Discussion - Repeated dose Tissue distribution study

• On 16 Mar 2012 at 11:20:19, "Wang, Bonnie" (bonnie.wang.-at-.bms.com) sent the message
  

  
  For certain long half-life compounds, we will have to run a repeated dose tissue
  distribution study according to ICH guideline "Guidance for repeated dose tissue
  distribution studies". The duration of those type of studies is typically 1 to 3
  weeks and radiolabeled compounds are typically used. Due to the limit amount of
  radiolabeled compounds, I wonder if we can pretreat the animals with
  non-radiolabels compounds until the steady state is achieved...  and then, treat
  the animals with radiolabeled compounds to get the tissue distribution data. Any
  concerns?
  
  Thanks.
  
  Bonnie Wang
  Research Scientist
  USA
  
  [Interesting one for the tracer kinetics people. My first guess is no, you would
  need to get the radiolabeled compound at steady state too - db]
  

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• On 16 Mar 2012 at 18:35:52, "Stumpf, Walter E" (stumpfwe.-at-.email.unc.edu) sent the message
  

  
  The following message was posted to: PharmPK
  
  Nota bene:
  In general, tissue distribution studies with conventional biochemical tissue
  dissection and with whole body autoradiography alone are inadequate. Tissue
  resolution is lacking and tissue heterogeneity is ignored. High specificity-low
  capacity sites of receptor binding and deposition frequently remain
  undiscovered, resulting in false negatives. Thus, important information on
  target tissues may be missing, leading to erroneous decisions (e.g., blood-brain
  barrier). This has been documented and discussed extensively in the literature.
  Implications are largely ignored and tolerated by the FDA.
  
  Walter E. Stumpf
  Dr.med., Ph.D., Dr.h.c.
  Professor of Cell Biology and Pharmacology em.
  University of Chapel Hill
  

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• On 17 Mar 2012 at 06:53:18, "Kishore Katyayan (Khan)" (kishore0123.-a-.gmail.com) sent the message
  

  
  The following message was posted to: PharmPK
  
  Because of the presence of  non-radioactive compound in these
  pretreated animals, specific activity of the radioactive compound will
  change once it is dosed to the same animals and it will be difficult
  to get any reliable data.
  
  Thanks,
  
  Kishore
  
  

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