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To all,
This is a question related to treatment of blood samples in PK studies
with prodrugs (esters) dosed orally. Am interested in knowing of types
of esterase inhibitors that are used (if any) , in what manner, when etc
and what concentrations. Would be interested in hearing any
experiences.......
Sara Kenkare
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[Two replies - db]
From: DGarg8838.aaa.aol.com
Date: Wed, 18 Aug 1999 18:02:44 EDT
Subject: Re: PharmPK treatment of ester prodrug dosing PK blood samples
To: PharmPK.at.boomer.org
In the work we did many years back, we used Sodium Fluoride as an
inhibitor.in concentration range of 6-8 mg/ml. This concentration was used t=
o
prevent invitro hydrolysis of methylprednisolone acetate to
methylprednisolone. The paper is listed below:
Dyal C. Garg, Philip Ng, Donald J. Weidler, Ermelinda Sakmar and John G.
Wagner, " Preliminary In Vitro and In Vivo Investigations on
Methylprednisolone and its Acetate", Research Communications in Chemical
Pathology and Pharmacology, Vol 22, 1978, pages 37-48.
Please contact me at the following if I can provide any additional help.
Dyal Garg, Ph.D.
Clinical Research Services, Inc.
Phone: 561-737-3954
Fax: 561-732-1941
E-mail:Dgarg8838.at.aol.com
---
From: Bernhard.Ladstetter.aaa.merck.de
X-Internal-ID: 37B0459D00011085
X-Lotus-FromDomain: MERCK
To: PharmPK.-a-.boomer.org
Date: Wed, 18 Aug 1999 08:48:13 +0200
Subject: Antwort: PharmPK treatment of ester prodrug dosing PK blood
samples
Sara:
We are using dichlorvos (2,2-dichlorovinyldimethylphosphate) at a
concentration of 1mg/mL. 10 =B5L of this solution are pipetted into the bloo=
d
collection tubes prior to blood sampling (together with an anticoagolant
like citrate or EDTA if plasma is generated). This amount is sufficient for
5-10 mL of whole blood. Plasma should be generated at 4=BAC. Like other
organophosphates this works well for ester prodrugs. Be careful as these
agents are quite toxic! An in-vitro test with blank plasma and plasma with
dichlorvos spiked with your prodrug should be done in advance.
Regards,
Bernhard
Bernhard J. Ladstetter, PhD
Institute of Pharmacokinetics & Metabolism
Merck KGaA
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Copyright 1995-2010 David W. A. Bourne (david@boomer.org)