Drug Metabolism Letters

Zhiyang Zhao
Amgen
Cambridge, MA
USA

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Application of Modern Drug Metabolism Structure Determination Tools and Assays to the In Vitro Metabolism of Imiloxan

Author(s): William L. Fitch, Yuan Chen, Liling Liu, Axel Paehler, May Young.

Abstract:

Imiloxan is an alpha2 adrenoceptor antagonist and was developed for depression in the 1980s. In Phase 1 clinical trials imiloxan dosing led to hypersensitivity reactions; the molecules development was discontinued. The present study revisits the in vitro metabolism of imiloxan using modern analytical methods. Human and rat liver microsomes convert imiloxan into a variety of metabolites many of which are unstable and or reactive. Imiloxan also yields high protein covalent binding in microsomal assays. Imiloxan is a useful test molecule for defining the relationship between liver covalent binding and idiosyncratic toxicity.

Keywords: Imiloxan, metabolism, mass spectrometry, reactive metabolite

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Article Details

VOLUME: 4
ISSUE: 2
Year: 2010
Page: [77 - 87]
Pages: 11
DOI: 10.2174/187231210791292753
Price: $58