PharmPK Discussion - MTX in pediatric patients

• On 20 May 2011 at 04:54:05, ehab eldesoky (ehegypt.at.yahoo.com) sent the message
  

  
  Dear ALL,
  In the light of high dose MTX in pediatric patients with blood  malignancy, Do you agree with the trend of prediction of MTX  concentration and not to wait 24 to 48h till TDM of MTX is obtained? If  yes, how to predict? what sampling time is then recommended? How many  sample we should obtain?
  We don't want to wait the MTX conc at 24 or 48 h to decide to start  leucovorine because sometimes patients develop mucositis. Thanks in advance!
  Prof Ehab S. EL Desoky
  Prof of pharmacology
  Faculty of Medicine
  Assiut University
  Assiut, Egypt
  
  

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• On 20 May 2011 at 18:34:47, Roger Jelliffe (jelliffe.-a-.usc.edu) sent the message
  

  
  The following message was posted to: PharmPK
  
  Dear Ehab:
  
    A good comment. MTX has had a checkered past because all people have
  been interested in is when to get samples to decide if a patient needs
  leukovorin or not. That is extremely poor experimental design for making a
  model which captures AUC with any reliability. The earliest I have seen MTX
  sampled is 8 hours after a dose. Because of this, there is no really
  reliable information from which to compute a good AUC, but people still
  treat to a target AUC even though it is so unreliable.
  
    I would suggest that what is needed first is a reliable population
  model of MTX. People say it is "rapidly distributed" , but no one, to my
  knowledge, has obtained any data to evaluate this. I think what is needed is
  a sampling strategy something like 1, 2, 4, 6, 8, 12, and 24 hours after a
  dose. Then, as you go along, make a population model after 5 patients, and
  do D-optimal design on the parameter values you get. Assume a 2 compartment
  model with a Ka, Vc, Vp, KCP and Kpc, and Kel. Recalculate this after every
  5 patients, until you have at least 50 total. Then you should have, probably
  for the first time, a reliable pop model for MTX. Then you will also have a
  good strategy formulated for optimal TDM.
  
  Does this help?
  
  All the best,
  
  Roger Jelliffe
  
  

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