Simultaneous Assessment of Pharmacokinetics of Pilsicainide Transdermal Patch and Its Electropharmacological Effects on Atria of Chronic Atrioventricular Block Dogs

Hiroshi Iwasaki; Akira Takahara; Yuji Nakamura; Yoshioki Satoh; Takeshi Nagai; Norihiro Shinkai; Atsushi Sugiyama

doi:10.1254/jphs.09061SC

Short Communications

Simultaneous Assessment of Pharmacokinetics of Pilsicainide Transdermal Patch and Its Electropharmacological Effects on Atria of Chronic Atrioventricular Block Dogs

Hiroshi Iwasaki, Akira Takahara, Yuji Nakamura, Yoshioki Satoh, Takeshi Nagai, Norihiro Shinkai, Atsushi Sugiyama

Author information

Hiroshi Iwasaki
Department of Pharmacology, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Japan
Akira Takahara
Department of Pharmacology, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Japan
Yuji Nakamura
Department of Pharmacology, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Japan
Yoshioki Satoh
Department of Pharmacology, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Japan
Takeshi Nagai
Research & Development Department, Nipro Patch Co., Ltd., Japan
Norihiro Shinkai
Research & Development Department, Nipro Patch Co., Ltd., Japan
Atsushi Sugiyama
Department of Pharmacology, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Japan
Yamanashi Research Center of Clinical Pharmacology, Japan

Keywords: pilsicainide, transdermal delivery, atrial fibrillation

JOURNAL FREE ACCESS

2009 Volume 110 Issue 3 Pages 410-414

DOI https://doi.org/10.1254/jphs.09061SC

View "Advance Publication" version (July 3, 2009).

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Abstract

Pharmacokinetics of pilsicainide transdermal patch and its electropharmacological effects were simultaneously assessed using chronic atrioventricular block dogs. After application of the patch (9.8 mg/kg), pilsicainide was continuously absorbed through the skin with a C_max of 0.49 ± 0.13 μg/ml, while its plasma concentration was kept above the clinically reported minimum effective plasma concentration for 2 – 8 h. Inter-atrial conduction time was significantly prolonged, whereas statistically significant prolongation was not detected in the atrial effective refractory period. Prolongation of the cycle length of atrial fibrillation and anti-fibrillatory action were confirmed. Thus, pilsicainide can be absorbed transdermally to exert long-lasting electropharmacological effects leading to anti–atrial fibrillatory action.

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