Assessment of the inactivation potential of desethylamiodarone on human CYP1A1.

Marwa E Elsherbiny, Ayman O S El-Kadi, Dion R Brocks

Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada T6G 2N8.

Drug metabolism letters 2010 Jan

filter terms:

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 microM and 9.6 microM, respectively) of CYP1A1 by desethylamiodarone. NADPH addition and/or replenishment were found to be important factors in determining the control activity in inactivation studies.

Citation

Marwa E Elsherbiny, Ayman O S El-Kadi, Dion R Brocks. Assessment of the inactivation potential of desethylamiodarone on human CYP1A1. Drug metabolism letters. 2010 Jan;4(1):9-14