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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
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[Two replies - db]
Date: Wed, 18 Aug 1999 18:02:44 EDT
Subject: Re: PharmPK treatment of ester prodrug dosing PK blood samples
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=
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.
Date: Wed, 18 Aug 1999 08:48:13 +0200
Subject: Antwort: PharmPK treatment of ester prodrug dosing PK blood
We are using dichlorvos (2,2-dichlorovinyldimethylphosphate) at a
concentration of 1mg/mL. 10 =B5L of this solution are pipetted into the bloo=
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.
Bernhard J. Ladstetter, PhD
Institute of Pharmacokinetics & Metabolism
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