Kosuke Doki1, Yuki Shirayama2, Yukio Sekiguchi3, Kazutaka Aonuma3, Yukinao Kohda2, Masato Homma2. 1. Department of Pharmaceutical Sciences, Faculty of Medicine, University of Tsukuba, Tennodai 1-1-1, Tsukuba, Ibaraki, 305-8575, Japan. k-doki@md.tsukuba.ac.jp. 2. Department of Pharmaceutical Sciences, Faculty of Medicine, University of Tsukuba, Tennodai 1-1-1, Tsukuba, Ibaraki, 305-8575, Japan. 3. Department of Internal Medicine, Faculty of Medicine, University of Tsukuba, Tennodai 1-1-1, Tsukuba, Ibaraki, 305-8575, Japan.
Abstract
PURPOSE: The clinical usefulness of therapeutic drug monitoring (TDM) of propafenone, a sodium channel blocker, has been unclear due to the lack of information regarding optimal blood sampling time and therapeutic concentration range. Antiarrhythmic effects of sodium channel blockers are affected by the activity of the cardiac sodium channel (SCN5A). We investigated the optimal sampling time and the clinical implication of the SCN5A promoter haplotype in propafenone TDM. METHODS: We evaluated serum concentrations of propafenone, the SCN5A promoter haplotype, and antiarrhythmic efficacy in 55 patients with supraventricular tachy-arrhythmias. Blood samples obtained 1.5-6 and 10-24 h after the last dose were categorized as peak and trough samples, respectively. RESULTS: The peak propafenone concentration was significantly higher in effectively treated patients than that in patients showing insufficient response (337 ± 213 vs. 177 ± 93 ng/mL, P = 0.005), but the trough propafenone concentration was not significantly different between the two groups (68 ± 48 vs. 42 ± 36 ng/mL). Clinically relevant propafenone efficacy was achieved significantly more often in SCN5A haplotype B carriers than in wild-type haplotype A homozygotes (90 vs. 60%, P < 0.05). Among the haplotype A homozygotes, peak propafenone concentration was higher in effectively treated patients than that in patients showing insufficient response (299 ± 177 vs. 177 ± 93 ng/mL, P = 0.061). CONCLUSION: The present study found that antiarrhythmic efficacy of propafenone was associated with peak propafenone concentration rather than trough concentration and was affected by the SCN5A promoter haplotype.
PURPOSE: The clinical usefulness of therapeutic drug monitoring (TDM) of propafenone, a sodium channel blocker, has been unclear due to the lack of information regarding optimal blood sampling time and therapeutic concentration range. Antiarrhythmic effects of sodium channel blockers are affected by the activity of the cardiac sodium channel (SCN5A). We investigated the optimal sampling time and the clinical implication of the SCN5A promoter haplotype in propafenone TDM. METHODS: We evaluated serum concentrations of propafenone, the SCN5A promoter haplotype, and antiarrhythmic efficacy in 55 patients with supraventricular tachy-arrhythmias. Blood samples obtained 1.5-6 and 10-24 h after the last dose were categorized as peak and trough samples, respectively. RESULTS: The peak propafenone concentration was significantly higher in effectively treated patients than that in patients showing insufficient response (337 ± 213 vs. 177 ± 93 ng/mL, P = 0.005), but the trough propafenone concentration was not significantly different between the two groups (68 ± 48 vs. 42 ± 36 ng/mL). Clinically relevant propafenone efficacy was achieved significantly more often in SCN5A haplotype B carriers than in wild-type haplotype A homozygotes (90 vs. 60%, P < 0.05). Among the haplotype A homozygotes, peak propafenone concentration was higher in effectively treated patients than that in patients showing insufficient response (299 ± 177 vs. 177 ± 93 ng/mL, P = 0.061). CONCLUSION: The present study found that antiarrhythmic efficacy of propafenone was associated with peak propafenone concentration rather than trough concentration and was affected by the SCN5A promoter haplotype.
Authors: Connie R Bezzina; Wataru Shimizu; Ping Yang; Tamara T Koopmann; Michael W T Tanck; Yoshihiro Miyamoto; Shiro Kamakura; Dan M Roden; Arthur A M Wilde Journal: Circulation Date: 2006-01-16 Impact factor: 29.690
Authors: L Frabetti; B Marchesini; A Capucci; C Cavallini; S Gubelli; E Ambrosioni; B Magnani Journal: Eur J Clin Pharmacol Date: 1986 Impact factor: 2.953
Authors: L A Siddoway; K A Thompson; C B McAllister; T Wang; G R Wilkinson; D M Roden; R L Woosley Journal: Circulation Date: 1987-04 Impact factor: 29.690