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The following message was posted to: PharmPK
here where I write, I do not have normal value tables available but alkaline
phosphatase is normally in children higher than in adults and even in
newborns should be sufficient to activate etopophos. The capacity normally
far exceeds the substrate concentrations.
The rapid activation is the reason for the need of specific blood sampling
with enzym inhibition.
The problem with etoposid is that the first and widely distributed
preparations contained benzylalcohol and ethanol to an high extend.
The first is strictly contraindicated during the first weeks of
life.(Gasping syndrome)
We, therefore, use on routine base etopophpos in the first year of life and
in high dose treatment protocols. In the few samples we tested in children,
the etoposide levels were comparable to the use of standard drug. All the
literature reports comparable pk because of the highest amounts of
phosphatase activity in circulating blood.
If there were a limited delay in deliberation, however, this should be of no
interest clinically, as there is not such a strong correlation of pk to pd.
The urinary fraction could increase a bit but dose calculation on square
meter bases always is only an rough approximation .
If there is any doubt, dont hesitate to send us samples for the measurement
of etopophos (EDTA) or total etoposide (Serum) or both (EDTA). Leipzig is
not very far from here and we offer the monitoring for all pediatric
oncology trials for most of the active drugs.
hope this may help,
joachim Boos
Dept Pediatric Oncology
Univ. M=FCnster
Germany
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Copyright 1995-2010 David W. A. Bourne (david@boomer.org)