PharmPK Discussion - Intracellular concentration in tissues

• On 8 Mar 2007 at 02:19:43, Nandu (nandudhabale2000.-at-.yahoo.com) sent the message
  

  
  Hello all of you,
  I am working on a disease where there are no disease animal models.
  Invitro activity is already establised. so the closest estimate of
  the drug efficacy is in the intracellular tissue concentration. we
  have already done the whole tissue levels.. but we want to know the
  intracellular levels of the compound achieved after oral dosing. I
  wanted to know if any one has done such studies before and if any one
  can share their experience it will be very helpful.
  Thank you,
  Dr.Nandu Dhabale
  
  

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• On 9 Mar 2007 at 12:41:48, "sankaratata" (sankaratata.-a-.indiatimes.com) sent the message
  

  
  Dear Dr.Nandu,
  Previously long ago, we are successful by using a test NDDS
  formulation by tagging the API with Radiolabelled compound.
  You too can try that.
  Santosh Tata
  Bioanalytical Division, BEC
  Apotex Inc, Bangalore
  
  

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• On 9 Mar 2007 at 08:42:34, "BENECH Henri 137577" (Henri.BENECH.-a-.cea.fr) sent the message
  

  
  The following message was posted to: PharmPK
  
  Dear Nandu Dhabale,
  What kind of tissue/cells have you worked with?
  
  Many intracellular studies have been done on circulating blood cells
  (like peripheral blood mononuclear cells) easy to collect. Our group
  has performed such studies as:
  
  Antimicrob Agents Chemother. 2005 May;49(5):1907-14.   Pruvost A, et al.
  
  AIDS. 2004 Jan 23;18(2):181-7.  Becher F et al.
  
  Hope this help
  
  Henri BENECH
  CEA, France
  email: henri.benech.-a-.cea.fr
  
  

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• On 9 Mar 2007 at 05:22:54, stumpfwe.aaa.email.unc.edu sent the message
  

  
  The following message was posted to: PharmPK
  
  Dear Dr. Nandu Dhabale
  
  For the cellular in vivo localization of a drug, magnification of
  tissue sections is necessary - unless you homogenize; but then you
  are unable to attribute it to certain cells and dissociate non-
  covalently bound drug from the receptor.
  Please consider:
  Stumpf WE, Drug Localization and Targeting with Receptor Microscopic
  Autoradiography. Journal of Pharmacological and Toxicological Methods
  51(2005):25-40.
  Stumpf WE. Drug Localization in Tissues and Cells. IDDC Press, Chapel
  Hill, NC, 2003
  (www.walterstumpf.com)
  
  Walter Stumpf, Chapel Hill, NC
  
  

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• On 11 Mar 2007 at 14:22:58, "Walt Woltosz" (walt.aaa.simulations-plus.com) sent the message
  

  
  The following message was posted to: PharmPK
  
  You might consider using PBPK modeling to predict the concentration in
  various tissues. Partition coefficients (Kp's) can be estimated from
  plasma
  protein binding and logP/logD. In our experience, distribution can
  usually
  be estimated within a reasonable ballpark this way. Clearance is another
  matter. If you have a good measure of in vitro clearance, it can
  often be
  scaled to provide a good estimate of in vivo clearance.
  
  Absorption and bioavailability can be predicted within a reasonable
  range if
  you have a passively diffused drug. If you have a transporter (influx or
  efflux) substrate, then some measure of the transporter affinity will
  also
  be needed to estimate absorption rate.
  
  Walt Woltosz
  Chairman & CEO
  Simulations Plus, Inc. (AMEX: SLP)
  42505 10th Street West
  Lancaster, CA  93534-7059
  U.S.A.
  http://www.simulations-plus.com
  Phone: (661) 723-7723
  FAX:   (661) 723-5524
  E-mail: walt.at.simulations-plus.com
  
  

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