Assessment of the inactivation potential of desethylamiodarone on human CYP1A1.
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.
Elsherbiny
Marwa E
ME
Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada T6G 2N8.
El-Kadi
Ayman O S
AO
Brocks
Dion R
DR
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
D004791:Enzyme Inhibitors; D009249:NADP; D019363:Cytochrome P-450 CYP1A1; C036116:desethylamiodarone; D000638:Amiodarone