Atarashi H, Kuruma A, Yashima M, Saitoh H, Ino T, Endoh Y, Hayakawa H
First Department of Internal Medicine, Nippon Medical School, Tama-Nagayama Hospital, Tama-city, Tokyo, Japan.
Clin Pharmacol Ther. 2000 Aug;68(2):143-50. doi: 10.1067/mcp.2000.108733.
To elucidate pharmacokinetics and pharmacodynamics of landiolol hydrochloride, newer developed ultra-short-acting beta-blocker, in patients with various cardiac tachyarrhythmias.
The short duration of action and titratability of landiolol hydrochloride make it ideal for use in patients with a clinical need for beta-blockers.
In a total of 31 examinations we infused the drug in 19 patients (mean age, 55 +/- 14 years). After the persistence of the tachyarrhythmias was confirmed, continuous infusion was started at rates of 0.005, 0.01, 0.02, 0.04, and 0.08 mg/kg/min for 5 minutes (for paroxysmal atrial fibrillation, paroxysmal supraventricular tachycardia, and ventricular tachycardia) or 15 minutes (for ventricular premature complex). We analyzed the pharmacokinetics of 16 examinations. A one-compartment model provided a close fit for each blood concentration-time curve.
The maximum blood concentrations obtained clearly showed the dose dependency and revealed very short half-lives (range, 2.3 to 4.0 minutes). Area under the blood concentration-time curves also increased, showing dose dependency. In paroxysmal atrial fibrillation, landiolol hydrochloride reduced the heart rate from 111 +/- 20 to 90 +/- 10/min. Sinus rhythm was restored, without any adverse effects, in three of five patients with paroxysmal supraventricular tachycardia and one patient with ventricular tachycardia. There was no significant change in peripheral blood pressure.
Landiolol hydrochloride has a shorter elimination half-life than any other beta-blocker, and it can be administered safely to patients with various tachyarrhythmias.
阐明新型超短效β受体阻滞剂盐酸兰地洛尔在各种心脏快速性心律失常患者中的药代动力学和药效学。
盐酸兰地洛尔作用持续时间短且可滴定,使其成为临床上需要使用β受体阻滞剂的患者的理想选择。
在总共31次检查中,我们对19名患者(平均年龄55±14岁)输注了该药物。在确认快速性心律失常持续存在后,以0.005、0.01、0.02、0.04和0.08mg/kg/min的速率持续输注5分钟(用于阵发性心房颤动、阵发性室上性心动过速和室性心动过速)或15分钟(用于室性早搏)。我们分析了16次检查的药代动力学。单室模型与每条血药浓度-时间曲线拟合良好。
获得的最大血药浓度清楚地显示出剂量依赖性,并显示出非常短的半衰期(范围为2.3至4.0分钟)。血药浓度-时间曲线下面积也增加,显示出剂量依赖性。在阵发性心房颤动中,盐酸兰地洛尔使心率从111±20次/分钟降至90±10次/分钟。5例阵发性室上性心动过速患者中的3例和1例室性心动过速患者恢复了窦性心律,且无任何不良反应。外周血压无显著变化。
盐酸兰地洛尔的消除半衰期比任何其他β受体阻滞剂都短,并且可以安全地用于各种快速性心律失常患者。