Drug Metabolism Letters

Zhiyang Zhao
Amgen
Cambridge, MA
USA

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Assessment of the Inactivation Potential of Desethylamiodarone on Human CYP1A1

Author(s): Marwa E. Elsherbiny, Ayman O.S. El-Kadi, Dion R. Brocks.

Abstract:

Desethylamiodarone was reported to inactivate human CYP1A1. To assess this, two protocols were implemented employing dilution and non-dilution of the preincubation mixture. Inactivation studies performed with diluted preincubation mixtures showed no inactivation of CYP1A1 by desethylamiodarone. However there was evidence for a mixed competitive inhibition (competitive and the uncompetitive inhibition constants of 2.1 μM and 9.6 μM, respectively) of CYP1A1 by desethylamiodarone. NADPH addition and/or replenishment were found to be important factors in determining the control activity in inactivation studies.

Keywords: Desethylamiodarone, CYP1A1, metabolism, mechanism-based inhibition, inactivation, NADPH

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Article Details

VOLUME: 4
ISSUE: 1
Year: 2010
Page: [9 - 14]
Pages: 6
DOI: 10.2174/187231210790980462