Assessment of the Inactivation Potential of Desethylamiodarone on Human CYP1A1

Title: Assessment of the Inactivation Potential of Desethylamiodarone on Human CYP1A1

Volume: 4 Issue: 1

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

Affiliation:

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

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.

Cite this article as:

Elsherbiny E. Marwa, El-Kadi O.S. Ayman and Brocks R. Dion, Assessment of the Inactivation Potential of Desethylamiodarone on Human CYP1A1, Drug Metabolism Letters 2010; 4 (1) . https://dx.doi.org/10.2174/187231210790980462