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

Abstract

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 antifibrillatory action were confirmed. Thus, pilsicainide can be absorbed transdermally to exert long-lasting electropharmacological effects leading to anti-atrial fibrillatory action.

Impacts of Surgically Performed Renal Denervation on the Cardiovascular and Electrophysiological Variables in the Chronic Atrioventricular Block Dogs – Comparison With Those of Amiodarone Treatment –

“…reported to possess the structural and electrophysiological remodeling that may promote the occurrence and maintenance of atrial fibrillation. 16,[18][19][20] In this study, amiodarone prolonged the AERP, which supports the clinical efficacy of amiodarone in preventing the recurrence of atrial fibrillation. 24 In contrast, renal denervation was reported to reduce the duration of rapid pacing-induced atrial fibrillation in the pig, by which the AERP and P-wave duration were hardly affected.…”

Translational Studies on Anti-Atrial Fibrillatory Action of Oseltamivir by its in vivo and in vitro Electropharmacological Analyses

“…On the other hand, as another series of experiments, cardiovascular effects of 1 and 3 mg/kg of pilsicainide hydrochloride hydrate were assessed in the same manner (n = 4) as those for the middle and high doses of oseltamivir, respectively. We previously confirmed that the cardiohemodynamic and electrophysiological parameters in the in vivo experiments were stable > 2 h in the absence of pharmacological intervention ( Sugiyama and Hashimoto, 1998 ; Usui et al, 1998 ; Satoh et al, 1999 ; Iwasaki et al, 2009 ).…”

Assessment of drug‐induced proarrhythmias due to pilsicainide in patients with atrial tachyarrhythmias

“…However, in basic studies, pilsicainide was shown to block also the K + channels. Pilsicainide blocks the K + channel current in the human ether‐a‐go‐go‐related gene (HERG) with a preferential affinity for the open state of the channel, and shows a fast access to the binding site [18–20]. As a result, the K + channel blocking action of pilsicainide prolonged the QTc interval in patients presenting with very high pilsicainide concentrations.…”