PharmPK Discussion - IVIVC

• On 9 Jun 2012 at 06:43:51, David Bourne (david.at.boomer.org) sent the message
  

  
  Dear all,
  
  I am novice in the field of IVIVC and have some doubts regarding it.( I am
  currently using the IVIVC tool kit of WinNonLin.)
  
  1.) How many formulations are necessary for running  IVIVC in WinNonLin ?
      ( as per my knowledge three formulations are sufficient to fit the model )
  
  2.) Is it necesssary that the reference data is IV?
  
  3.) What is the difference between IVIVC and IVIVR ?
  
  Thanks
  shikha
  

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• On 9 Jun 2012 at 13:43:40, "LGibiansky.-a-.quantpharm.com" (LGibiansky.-at-.quantpharm.com) sent the message
  

  
  The following message was posted to: PharmPK
  
  Shikha,
  
  Q1 How many formulations are necessary for running  IVIVC in WinNonLin ?
    You can have as many or as few as you like for internal purposes; for
  regulatory, 3 is recommended (fast, slow, and medium dissolution rates)
  
  Q2 Is it necesssary that the reference data is IV?
  It can be (or even better to be) oral solution or immediate release oral
  formulation
  
  Q3 What is the difference between IVIVC and IVIVR ?
  Not sure; most likely, semantics
  
  Leonid
  
  

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• On 12 Jun 2012 at 15:13:06, shikha rawat (shikha06rawat.aaa.gmail.com) sent the message
  

  
  Hi Leonid,
  
  thanks for your reply.
  
  You can have as many or as few as you like for internal purposes; for
  regulatory, 3 is recommended (fast, slow, and medium dissolution rates)
  As per the guidelines by FDA it if the formulations are independent of various dissolution
  conditions like (pH, agitation) etc results from a single formulation are sufficient? but
  we still require a reference formulation for building IVIVC?
  It can be (or even better to be) oral solution or immediate release oral
  formulation
  Okay :-)
  
  thanks
  Shikha
  

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• On 28 Jul 2012 at 10:41:57, shikha rawat (shikha06rawat.-a-.gmail.com) sent the message
  

  
  Dear all forum members ,
  
   Has anyone of you tried forming IVIVC model for BCS class III drug?
  
  The data i currently have with me is ---
  1.) Fully replicated fasted in vivo data (RTRT,TRTR)  and in vitro data
  2.) Fully replicated fed study data (RTRT,TRTR) & in vitro data.
  
  My problem is -
  i tried to establish a model using IVIVC tool kit (taking only the first two periods in
  consideration). Weibull model was selected for fitting the in vitro disso data  and T was
  taken in the internal validation field . In the invivo tab R was taken in the reference
  field and the data type was oral. Maximum no of exponentials selected were 1 (by the
  visual inspection of the in vivo data)  strip Ka option was also selected. The first
  correlation model Fabs=Abs Scale * Disso (Tscale*Tvivo) was selected. The prediction error
  was quite large as shown below.
  
  Fromulation     Parameter  Predicted    Observed    PE(%)   Ratio
  T Internal           AUClast      134.80914   112.64871       19.7       1.20
                           Cmax         3.57053       5.58679         -36.1       0.64
  Avg Internal       AUClast    134.80914    112.64871        19.7       1.20
                           Cmax        3.57053       5.58679          36.1       0.64
  Is there something wrong in my approach & Does this high PE% mean that i cannot use this
  model for any prediction ? Also this study is not for the regulatory purposes but just for
  the investigation purposes of how well the disso and abs data are related.
  Any assistance is highly appreciated.
  
  thanks
  SR
  

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• On 28 Jul 2012 at 20:37:39, "Benet, Leslie" (Leslie.Benet.at.ucsf.edu) sent the message
  

  
  The following message was posted to: PharmPK
  
  Theoretically IVIVC should not work for Class 3 drugs, since the rate limiting step is not
  dissolution but intestinal permeability.
  In terms of BDDCS the rate limiting step for Class 3 drugs would be intestinal uptake
  transporters as modulated by intestinal efflux transporters.
  
  Leslie Z. Benet, Ph.D.
  Professor
  Department of Bioengineering & Therapeutic Sciences
  Schools of Pharmacy & Medicine
  University of California San Francisco
  533 Parnassus Avenue, Room U-68
  San Francisco, CA 94143-0912
  

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• On 31 Jul 2012 at 09:52:02, shikha rawat (shikha06rawat.at.gmail.com) sent the message
  

  
  Dear Dr Benet,
  thanks for your reply but i still have some queries.
  
  I recently read an article (Journal of Pharmaceutical sciences,Vol 90 1176 -
  1185 (2001))
  " IVIVC models for Metformin after administration of MR oral dosage forms to
  helathy volunteers " as per my knowledge Metformin is also a class III drug but
  still a valid IVIVC was built for that .
  
  Another important info my drug (X) has high solubility but low bioavailability
  (, also it is reported that it shows First pass effect)
  
  thanks
  SR
  
  

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