title: Influence of amiodarone on urinary excretion of 6beta-hydroxycortisol in humans.
abstract: The present study was undertaken to evaluate the use of cortisol 6beta-hydroxylation in defining the effect of amiodarone on cytochrome CYP3A activity. To accomplish this goal, the in vivo activity of CYP3A was estimated by measuring the 24-hour urinary excretion of 6beta-hydroxycortisol (6beta-OHC) and by calculating 24-hour ratio of 6beta-hydroxycortisol to urinary free cortisol (6beta-OHC/UFC ratio). Nine cardiac patients scheduled for amiodarone treatment were recruited to participate in this study. Urine was collected over a 24-hour period from each subject before the first amiodarone administration and during the third day of oral administration of amiodarone (200 mg four times daily as a loading dose). Three days of amiodarone treatment caused a significant decrease (p<0.05) in both the 6beta-OHC/UFC ratio and the 24-hour urinary excretion of 6beta3-OHC. These results suggest that amiodarone is an inhibitor of CYP3A activity.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Charles University, Hradec Krdlávé, Czech Republic. micuda@lfhk.cuni.cz
authors.forename: S
authors.initials: S
authors.lastname: Micuda
authors.forename: M
authors.initials: M
authors.lastname: Hodac
authors.forename: L
authors.initials: L
authors.lastname: Sispera
authors.forename: P
authors.initials: P
authors.lastname: Parízek
authors.forename: M
authors.initials: M
authors.lastname: Pleskot
authors.forename: G
authors.initials: G
authors.lastname: Zimova
authors.forename: J
authors.initials: J
authors.lastname: Cerman
authors.forename: J
authors.initials: J
authors.lastname: Martínková
authors.forename: V
authors.initials: V
authors.lastname: Pidrman
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000638:Amiodarone / Q000008:administration & dosage*; D001189:Aryl Hydrocarbon Hydroxylases; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D006801:Humans; D006854:Hydrocortisone / Q000031:analogs & derivatives* / Q000652:urine*; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000188:drug therapy* / Q000378:metabolism; D010089:Oxidoreductases, N-Demethylating / Q000378:metabolism; D014665:Vasodilator Agents / Q000008:administration & dosage*
chemical_list: D014665:Vasodilator Agents; C001380:6 beta-hydroxycortisol; D003577:Cytochrome P-450 Enzyme System; D001189:Aryl Hydrocarbon Hydroxylases; D051544:Cytochrome P-450 CYP3A; D010089:Oxidoreductases, N-Demethylating; D000638:Amiodarone; D006854:Hydrocortisone