Abstract
Objectives: Pilsicainide, an anti-arrhythmic agent of class Ic of the Vaugham Williams 4-level schema, is reported to be safe and effective in the treatment of perioperative supraventricular arrhythmia. We investigated the effects and pharmacokinetics of intravenous administration of pilsicainide on supraventricular arrhythmias in patients after esophageal cancer surgery. Subjects and methods: After obtaining Institutional Review Board approval and informed consent, 0.75 mg/kg of pilsicainide hydrochloride for injection was administered in 10 minutes to 8 patients who developed supraventricular arrhythmia (2: paroxysmal atrial fibrillation, 2: paroxysmal supraventricular tachycardia, 4: premature atrial contractions≥10/min) after esophageal cancer surgery. Blood samples were collected prior to, and 10, 20, 30, 40, 50, 60, 120, 240, 480 minutes after pilsicainide administration. The plasma pilsicainide concentration was determined by high-performance liquid chromatography. The pharmacokinetic parameters were obtained using a 2-compartment model and compared with those of healthy adults (1). Results: Pilsicainide successfully terminated supraventricular arrhythmia in 6 of 8 patients. No adverse effects, such as hypotension and abnormal ECG pattern, were observed. The maximum plasma concentration (Cmax) of pilsicainide was 2.07±0.59 [mean±SD (standard deviation)] μg/ml, which was significantly higher than that of the healthy adults (1.20±0.16μg/ml). The half-life of α-phase (t1/2α) was significantly prolonged, and the volume of distribution at the steady state (Vdss) and the volume of the peripheral compartment (V2) were significantly decreased. Discussion and Conclusion: Since a single injection of pilsicainide was suggested to be effective for treatment of supraventricular arrhythmia after esophageal cancer surgery, changes in pharmacokinetic parameters warranted the closest attention to avoid relative overdose and adverse effects.
