title: Combined administration of quinidine and propafenone for atrial fibrillation: the CAQ-PAF study.
abstract: Propafenone and its 5-hydroxy metabolite exhibit different electrophysiological properties. Objectives of the CAQ-PAF study were (1) to develop a strategy favoring propafenone instead of 5-hydroxypropafenone in plasma following oral administration of propafenone and (2) to evaluate the potential of low-dose quinidine to chronically inhibit CYP2D6. Patients (n = 102) with atrial fibrillation received propafenone 150 mg 3 times daily with either quinidine 100 mg twice daily or placebo. Throughout the study (follow-up, 199 ± 155 days), quinidine successfully inhibited CYP2D6: propafenone concentrations were 3 times higher in patients receiving quinidine (1033 ± 611 ng/mL vs 328 ± 229 ng/mL; P < .001). Moreover, 80% (n = 10) of patients with propafenone levels greater than 1500 ng/mL were in sinus rhythm at 1 year. In contrast, recurrence of atrial fibrillation occurred in 22 of 23 patients with propafenone levels less than 1000 ng/mL (P < .0001). Thus, chronic inhibition of CYP2D6 is achievable with low-dose quinidine in humans. Increased plasma levels of propafenone may be highly beneficial to prevent recurrence of atrial fibrillation.
authors.affiliation: Institut universitaire de Cardiologie et de Pneumologie, Québec, Québec, CanadaFaculty of Medicine, Université Laval, QuébecCRCHUM, Centre Hospitalier de l'Université de Montréal and Faculty of Pharmacy, Université de Montréal, Montréal, Quebec, CanadaCentre Hospitalier Région de l'Amiante, Thetford Mines, Québec, Canada.
authors.forename: Gilles E
authors.initials: GE
authors.lastname: O'Hara
authors.forename: François
authors.initials: F
authors.lastname: Philippon
authors.forename: Marcel
authors.initials: M
authors.lastname: Gilbert
authors.forename: Jean
authors.initials: J
authors.lastname: Champagne
authors.forename: Véronique
authors.initials: V
authors.lastname: Michaud
authors.forename: Lyne
authors.initials: L
authors.lastname: Charbonneau
authors.forename: Guylaine
authors.initials: G
authors.lastname: Pruneau
authors.forename: Bettina A
authors.initials: BA
authors.lastname: Hamelin
authors.forename: Peter
authors.initials: P
authors.lastname: Geelen
authors.forename: Jacques
authors.initials: J
authors.lastname: Turgeon
mesh_terms: D000368:Aged; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics; D001281:Atrial Fibrillation / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics / Q000378:metabolism; D065690:Cytochrome P-450 CYP2D6 Inhibitors / Q000008:administration & dosage*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D011405:Propafenone / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics; D011802:Quinidine / Q000008:administration & dosage*
chemical_list: D000889:Anti-Arrhythmia Agents; D065690:Cytochrome P-450 CYP2D6 Inhibitors; D011405:Propafenone; D019389:Cytochrome P-450 CYP2D6; D011802:Quinidine