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Date: Wed, 10 Jun 1998 08:43:19 +0200
From: "Dr. Bernhard Ladstetter"
Reply-To: Lstetter.aaa.merck.de
Organization: merck.de
MIME-Version: 1.0
To: PharmPK.aaa.pharm.cpb.uokhsc.edu
Subject: Prodrug stability
Hi Majid,
we have performed similar studies as the one you are planning. We always
used plasma instead of blood, well knowing that also RBC=B4s can
contribute to ester hydrolysis (AChE).Our experience is that also
monkeys can be different from man in terms of ester hydrolysis in-vitro.
The question is about the relation to the situation you find in-vivo.
What happens in gut wall and in the liver? For ester-prodrugs we used
this approach: stability in plasma of lab animals (the one you use in
pharmacology and tox), stability in simulated gastric and intestinal
fluid, then pilot PK in vivo in rat and dog and/or monkey.
I hope that helps,
regards,
Bernhard
Bernhard J. Ladstetter
-----------
Institute of Pharmacokinetics and Metabolism
Merck KGaA, Germany
e-mail: Lstetter.-a-.merck.de
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From: Adrienne Sips
To: PharmPK.aaa.pharm.cpb.uokhsc.edu
Date: Wed, 10 Jun 1998 09:16:17 +0200
Subject: Prodrug stability
Mime-Version: 1.0
I am interested in all kinds of tests simulating the digestion processes in
the gastrointestinal tract. Could you send me information about the
'simulated gastric juice' you are going to apply?
With kind regards,
Adrienne Sips, PhD
Head Experimental Validation
Laboratory of Exposure Assessment
National Institute of Public Health & the Environment
PO Box 1
3720 BA Bilthoven
The Netherlands
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We use Gastric Fluid, Simulated, TS (USP XXI):
Dissolve 2.0 g of sodium chloride and 3.2 g of Pepsin in 7.0 mL of
hydrochloric acid and sufficient water to make 1000 mL. The test
solution has a pH of about 1.2.
Comment: we prepare only 1/100 to 1/10 of this volume.
Best regards,
Bernhard J. Ladstetter, PhD
Institute of Pharmacokinetics and Metabolism
Merck KGaA, Germany
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