抗不整脈薬ｆｌｅｃａｉｎｉｄｅ ａｃｅｔａｔｅの生体内薬物動態と心室期外収縮抑制効果

Abstract

To study the pharmacokinetics of flecainide acetate (FLC) and its suppressive effects on ventricular premature contractions (VPC), twenty-five patients with frequent VPCs were studied following single oral administration method. Either one of the dosages of 100 mg, 200 mg, or 300 mg of FLC was administered and blood samples were drawn before and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, and 48hr after the drug administration to measure the plasma drug concentration using high-performance liquid chromatography. Standard 12-lead ECG and 24-hr dynamic ECG were recorded to assess the effects on VPC and ECG parameters.The maximum plasma concentration (Cmax) and the area under the time-concentration curve (AUC) increased in a dose-dependent manner and there was a linear relationship between the dose and Cmax or AUC (P<0.01).The time of Cmax (Tmax: 3.0 to 4.0 hr) and the plasma half-life in the elimination phase (t1/2: 12to15hr) were independent of the dose.The suppressive effects on VPC were assessed in 20 patients who had more than 5, 000 VPCs/day before drug administration (baseline). The reduction of more than 75% of the baseline frequency of VPC was found in 13 of the patients studied (65%), and the effects on VPCs increased in a dose-dependent manner (100mg, 50%; 200mg, 63%; 300mg, 80%).The minimum effective plasma concentration was 197.1ng/ml to 303.8 ng/ml. Blood pressure or ECG parameters showed no significant changes after the drug administration. No serious side effects were found in any patients. In conclusion, , FLC possesses a long plasma half-life and a linear pharmacokinetics. The suppressive effects on VPCs increased in a dose-dependent manner, and the minimum effective plasma concentration to suppress VPCs was considered to be 200-300ng/ml.