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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
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The following message was posted to: PharmPK
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,
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