Development of acetaminophen proline prodrug

Document Type

Article

Publication Date

2010

Abstract

In this research work, proline ester prodrug of acetaminophen (Pro-APAP) was synthesized and evaluated for its stability in PBS buffer at various pH and Caco-2 cell homogenate. The Pro-APAP is more stable at lower pH than higher pH, with half-life of 120 min in PBS buffer at pH 2.0, half-life of 65 min at pH 5.0, and half life of 3.5 min at pH 7.4, respectively. The half-life of Pro-APAP in Caco-2 cell homogenate is about 1 min, much shorter than the half-life in PBS buffer at pH 7.4, indicating enzymes in the cell homogenate contribute to the hydrolysis of the ester bond. Carboxypeptidase A was incubated with Pro-APAP at pH 7.4 with half-life of 3.8 min which is very close to the half life in buffer itself. This clearly indicates carboxypeptidase A is not one of the enzymes contributing to the hydrolysis of the prodrug. Physicochemical characteristics such as melting point and stability of newly synthesized prodrug were determined by MDSC technique.

Publication Title

Bioorganic and Medicinal Chemistry Letters

Volume

20

Issue

13

First Page

3851

Last Page

3854

Comments

This article was published in Bioorganic and Medicinal Chemistry Letters, Volume 20, Issue 13, Pages 3851-3854.

The published version is available at http://dx.doi.org/10.1016/j.bmcl.2010.05.050.

Copyright © 2010 Elsevier.

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