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I have observed the following with a NCE. Dosing of the NCE in a co-
solvent formulation intravenously in rats leads to hematuria within a
few minutes. The NCE has low solubility and the problem is not
observed with vehicle alone. If the drug is prepared in a standard
Cremophor vehicle, hematuria is also not observed.
What is the mechanism that can lead to this problem? Is it due to
hemolysis in the blood or damage to the kidneys?
Cheers,
Damon Papac, SLC, UT
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Damon:
It sounds as if you are observing gross hematuria? Urinalysis will
help differentiate the etiology, you also need to know whether is it
actually heme you are seeing.
Sincerely,
Carol Collins MD
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Dear Damon,
simple way to decide whether you are dealing with hematuria or
hemoglobinuria includes
centrifugation of urine followed by analysis of the supernatant. If
the supernatant is red you are
dealing with hemoglobinuria (=> 0.5 g HB/L urine) or hemoglobinuria
and hematuria or mioglobinuria,
but hematuria alone is excluded. There is still possibility that
some red cells have been disrupted
due to inappropriate urine osmolality but this could be avoided if
you use fresh random urine
sample. You could also put urine sediment sample under the microscope
and look for red cells.
If you are still not sure whether you are dealing with hematuria due
to hemolysis you could
determine serum level of unconjugated bilirubin which is increased in
cases of intravascular
hemolysis. Depending on the resources that you have you could try to
determine serum activity of LDH
and AST. These enzyme activities and their ratio could also tell you
whether you are dealing with
intravascular hemolysis or not. However, in this case you could also
have superimposed liver damage
that can blur the picture defined by the changes of the given enzymes
and bilirubin.
It is not so easy to decide whether you are dealing with
mioglobinuria or hemoglobinuria. For that
you need some immunochemical tests. Some screening methods for this
purpose exist but I am not very
satisfied with them. If you have SE-HPLC system at your disposal
maybe you could differentiate MB
from HB based on mass difference. Myoglobinuria is also accompanied
by the rise of CK and creatinine
so you could analyze their activity/content in serum if you have
appropriate equipment at your
disposal.
Hope this helps.
Zeljko Debeljak, PhD student
Medical Biochemistry Specialist
Clinical Hospital Osijek,
CROATIA
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