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.
journal_name
J Clin Pharmacoljournal_title
Journal of clinical pharmacologyauthors
O'Hara GE,Philippon F,Gilbert M,Champagne J,Michaud V,Charbonneau L,Pruneau G,Hamelin BA,Geelen P,Turgeon Jdoi
10.1177/0091270011399574subject
Has Abstractpub_date
2012-02-01 00:00:00pages
171-9issue
2eissn
0091-2700issn
1552-4604pii
0091270011399574journal_volume
52pub_type
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