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Hello all,
I was just wondering if there was anyone in the group that could refer me
to information regarding the oral administration of Tween 80 formulations
in dogs. I have some pretty compelling information which argues against
formulations administered both i.v and i.m. but I am having difficulty
finding any references to oral admin. and oral absorption. Any help that
you could provide would be greatly appreciated.
Regards,
Danytza Ward
Bayer Corporation
PDM
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Hi,
I have experience about Tweens in dogs. I have personally dosed dogs
with a formulation containing Tween. All animals barely survived. They
had a very severe allergic reaction. Since this happened, I have been
looking for a document(s) recording this kind of reactions I think it
will be extremely important to have some information about excipients as
well.
Majid Vakily Ph.D.
Principal Research Scientist
DMPK-Discovery
Hoffmann La-Roche
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Dear Dr. Vakily:
The interaction of Tweens (80 or 20) is not surprising. Tweens produce
anaphylactic shock. This shock depends on dose. The formulations should be
diluted before intravenous administration. Oral dosing is not that a
problem.
Prasad Tata
Otsuka America Pharmaceutical, Inc.
2440 Research Blvd.
Rockville, MD 20850
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[Two more replies - db]
Date: Wed, 26 Aug 1998 14:28:08 -0600
From: Steven J. Weber
To: PharmPK.-at-.pharm.cpb.uokhsc.edu
Subject: PharmPK Re: Tween 80 -Reply
Mime-Version: 1.0
Request a copy of the MSDS from your supplier (or Sigma). The MSDS
will contain a list of references regarding toxic effects of Tween 80.
The exact cause of the toxic event may not be discussed.
Steve Weber, Ph.D.
Director, Met/PK
Oread, Inc
1-800-447-6501
---
Date: Wed, 26 Aug 1998 18:01:12 -0400
From: "Zutshi, Anup"
Subject: RE: PharmPK Tween 80
To: "'PharmPK.aaa.pharm.cpb.uokhsc.edu'"
We have successfully administered Tween 80 in oral formulations to dogs up
to a maximum concentration of 25% by weight with no adverse effects to the
animal. When the same is administered IV the animal will experience an
anaphylactoid reaction due to severe mast cell degranulation and subsequent
histamine release. We were able to minimize the effects of this histamine
release by pre-treating the animals with a H1/H2 receptor anatagonist
cocktail administered IM approximately 15 minutes prior to treatment. Of
course one needs to make sure that these drugs do not interfere with the
disposition of your test compound. Hemolysis is also a problem. Clinical
chemistry on these animals showed increased hepatic enzyme levels that
reverted back to baseline within 5 days.
Anup Zutshi
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