PharmPK Discussion - Physiological time - Dedrick plot

• On 17 Sep 2013 at 09:09:57, Alexander Bauer (alex05031988.at.hotmail.com) sent the message
  

  
  Dear all!
  
  I have some problems answering the question whether animal data are scaleable to predict human
  concentration time profiles or not.
  I have data from three different species plus human data at different dosing levels. My first
  problem is that data seem to violate dose proportionality assumption (which means that prediction
  within each species is not possible). So I think that my only option is to go on with the lowest
  dose levels and assume dose proportionality only for these levels. Or can I use all data for my
  analysis?
  
  I like the concept of physiological time and the complex dedrick plot as a graphical tool for the
  ability of data to predict human parameters. I generated a complex dedrick plot like it is described
  in Mahmood (2005), Interspecies Pharmacokinetic Scaling, page 226, using only the lowest dosing
  levels per animal species. The three curves are far away from overlapping, so can I conclude that my
  animal data can not be used for the predictation in humans as other between-species factors than
  physiological time exist?
  
  How can I predict PK parameters (e.g. Clearance) in man using the complex dedrick plot based on the
  three animal species data to check the observed human parameters with the predicted?
  
  Does anyone know the difference between the complex dedrick plot of Mahmood (2005) using simple
  allometric scaling for the exponents of clearance and volume of distribution and the complex dedrick
  plot of Gabrielsson and Weiner (2000), Pharmacokinetics and Pharmacodynamics, page 732, using a
  complex pharmacokinetic model for the estimation of the exponents of clearance and volme of
  distribution?
  
  If someone has any hints or comments regarding my analysis or my scope I would be very happy to hear
  them.
  
  Thanks for your help!
  Kind regards,
  Alexander
  
  [Maybe you should explore the departure from dose linearity between animals of the same species
  first. If it is metabolism related it may be difficult to 'scale' between species - db]
  
  

  Back to the Top

• On 17 Sep 2013 at 10:17:10, Hao Pan (haopan.-at-.gmail.com) sent the message
  

  
  Hi Alexander,
  
  If the dose proportionality assumption doesn't hold within a single
  species, chances are the pk is nonlinear. I could be wrong but I think
  dedrick plots work for linear pk scenarios.
  
  Hao
  
  [A reference that might be useful -
  http://ajpregu.physiology.org/content/ajpregu/245/6/R768.full.pdf
  Boxenbaum, H., & Ronfeld, R. (1983). Interspecies pharmacokinetic scaling and the Dedrick plots. The
  American journal of physiology, 245(6), R768–75. - db]
  
  

  Back to the Top

Copyright 1995-2014 David W. A. Bourne (david@boomer.org)