title: Assessment of the inactivation potential of desethylamiodarone on human CYP1A1.
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 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.
authors.affiliation: Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada T6G 2N8.
authors.forename: Marwa E
authors.initials: ME
authors.lastname: Elsherbiny
authors.forename: Ayman O S
authors.initials: AO
authors.lastname: El-Kadi
authors.forename: Dion R
authors.initials: DR
authors.lastname: Brocks
mesh_terms: D000638:Amiodarone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D019363:Cytochrome P-450 CYP1A1 / Q000037:antagonists & inhibitors*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D009249:NADP / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D009249:NADP; D019363:Cytochrome P-450 CYP1A1; C036116:desethylamiodarone; D000638:Amiodarone