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Combined Administration of Quinidine and Propafenone for Atrial Fibrillation: The CAQ‐PAF Study
Author(s) -
O'Hara Gilles E.,
Philippon François,
Gilbert Marcel,
Champagne Jean,
Michaud Véronique,
Charbonneau Lyne,
Pruneau Guylaine,
Hamelin Bettina A.,
Geelen Peter,
Turgeon Jacques
Publication year - 2012
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/0091270011399574
Subject(s) - propafenone , quinidine , atrial fibrillation , medicine , sinus rhythm , active metabolite , oral administration , cardiology , metabolite , pharmacology , anesthesia
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.