TITLE

Biomimetic modeling of oxidative drug metabolism

AUTHOR(S)
Lohmann, Wiebke; Karst, Uwe
PUB. DATE
May 2008
SOURCE
Analytical & Bioanalytical Chemistry;May2008, Vol. 391 Issue 1, p79
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
The prediction of drug metabolism is an important task in drug development. Besides well-established in vitro and in vivo methods using biological matrices, several biomimetic models have been developed. This review summarizes three different nonenzymatic strategies, including metalloporphyrins as surrogates of the active centre of cytochrome P450, Fenton’s reagent, and the electrochemical oxidation of drug compounds. Although none of the systems can simulate the whole range of cytochrome P450-catalyzed reactions adequately, the biomimetic models show some advantages over standard in vitro methods. For example, metalloporpyhrin catalysts allow the synthesis of certain metabolites in sufficient amounts and with sufficient purities to permit characterization and further pharmacological and toxicological tests. The electrochemical generation of metabolites coupled on-line to liquid chromatography/mass spectrometry is a promising tool for studying reactive metabolites and can be applied in automated high-throughput screening approaches. In this paper, detailed comparisons with cytochrome P450 catalysis are drawn, advantages and disadvantages of the respective methods are revealed, and possible applications are discussed.
ACCESSION #
31722437

 

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