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Good morning,
I have been researching using DMSO as a solvent for a compound in
in-vivo trials.
I have come across varying information from publications and on the
list serve.
If I am formulating an IV solution for a dog or non-human primate at
what concentration should I use the DMSO and what would the maximum
tolerated dosage for the animal be?
I hope that is a question that makes sense and can be answered.
I saw where people were saying up to 10% DMSO could be used and dosed
at like 2mg/kg, but I was unclear how they were using the solvent and
couldn't find a resource to verify the information.
I have heard where concentrations of 2% DMSO have caused severe
complication and death.
Thank you very much.
Loren C. Kohrs
Associate Scientist
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The following message was posted to: PharmPK
Loren,
your question makes sense for at least two reasons.
The FIRST is obviously the animal sensitivity to such an excipient.
Dogs are generally very sensitive!
The second is the relevance of such a formulation strategy regarding
the study goals. Whatever the max tolerated dose is I would argue that
more than 2% DMSO would expose your IV formulation to precipitation
issues and your study would not enable any realistic conclusion. If I
were you I would change my strategy.
with regards,
Frederic DOC (ex-Pfizer preformulation scientist)
ACRITER CONSULTING
7 rue montespan
91024 Evry cedex, FRANCE
http://www.acriter-consulting.com
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Dear sir:
I don't understand clearly about your argument "Whatever the max
tolerated dose is I would argue that more than 2% DMSO would expose your IV
formulation to precipitation issues and your study would not enable any
realistic conclusion." The 2% DMSO is corresponding to dog?or any animal?
Because I always use 10% DMSO in rat and mouse,and I never found any problems.
Thank you,
Jianw
Assoiate researcher
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The following message was posted to: PharmPK
Dear Jianw:
I do quite follow your argument. In one hand, you are
saying more than 2% DMSO in formulation will results
in precipitation and no realistic conclusions. In
other hand, you are using 10% DMSO with no problems.
Is it possible that you meant 20% DMSO? My question is
more around comparison of DMSO and DMA and a general
hesitation/negativity among formulation scientist in
using DMSO. Precipitation issue would be similar for
DMA as well. But say in a chronic 28 days Tox study I
rather to have DMSO in my formulation rather than DMA
(DMSO is better tolerated) but apparently not all
formulation people share this view. Philip starts
shading some light on this issue but I want to hear
more.
By the way Vuong, could not you mask the taste of DMSO
by adding flavour/sweetener? Beside, I think 17-AAG is
an anticancer agent so you are giving it orally?
Rostam
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The following message was posted to: PharmPK
DMSO is easily absorbed through skin, intestinal tract, etc. 17-AAG was
administered iv, and the effect is more severe. However, whichever the
route of administration, the DMSO will get to the taste buds and if you
worked with DMSO, you know how the taste hung around forever! It is bad
enough to cause noncompliance among patients. So if you have something
less noxious, such as Cremophor, you go for that.
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Copyright 1995-2010 David W. A. Bourne (david@boomer.org)