Pharmaceutical Sciences Faculty Publications

Characterization of In Vitro and In Vivo Metabolic Pathways of the Investigational Anticancer Agent, 2-Methoxyestradiol

Document Type

Article

Publication Date

7-1-2007

Journal Title

Journal of Pharmaceutical Sciences

ISSN

0022-3549

Volume

96

Issue

7

First Page

1821

Last Page

1831

DOI

10.1002/jps.20837

PubMed ID

17252610

Abstract

The aim of this study was to characterize the metabolic pathways of 2-methoxyestradiol (2ME2), an investigational anticancer drug. In vitro metabolism studies were performed by incubation of 2ME2 with human liver microsomes under various conditions and metabolite identification was performed using liquid chromatography-tandem mass spectrometry. In microsomal mixtures, four major oxidative metabolites and two glucuronic acid conjugates were observed originating from 2ME2. Human liver S9 protein fraction was used to screen for in vitro sulfation but no prominent conjugates were observed. The total hepatic clearance as estimated using the well-stirred model was approximately 712 mL/min. In vivo metabolism, assessed using 24-h collections of urine from cancer patients treated with 2ME2 revealed that

Keywords

Administration, oral, antineoplastic agents, biotransformation, Chromatography, high pressure liquid, drugs, investigational, estradiol, glucuronic acid, in vitro techniques, microsomes, liver, molecular structure, ovarian neoplasms, oxidation-reduction, prostatic neoplasms, tandem mass spectrometry

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