Howard P A
Department of Pharmacy Practice, University of Kansas Medical Center, Kansas City 66160, USA.
Ann Pharmacother. 1999 Jan;33(1):38-47. doi: 10.1345/aph.18097.
To discuss the clinical pharmacology of the antiarrhythmic drug ibutilide in patients with atrial fibrillation (AF) or atrial flutter (AFl).
A MEDLINE search (January 1983-December 1997) was used to identify pertinent English-language articles on ibutilide. Key search terms included ibutilide, AF, AFl, cardioversion, and sinus rhythm. The MEDLINE search was supplemented by references included in the bibliographies of comprehensive review articles and studies.
Studies and review articles describing the chemistry, pharmacology, and pharmacokinetics of ibutilide were selected. All abstracts and published clinical trials evaluating the efficacy and safety were reviewed.
Pertinent information on the pharmacology and mechanism of action of ibutilide was summarized. Data were extracted from the clinical trials describing trial design, patient population, interventions, methods of evaluation, outcomes, and statistical significance.
Ibutilide is a Vaughan-Williams class III antiarrhythmic agent approved for intravenous use for the rapid termination of recent-onset AF or AFl. The drug is extensively metabolized by the liver, has a volume of distribution of 11-15 L/kg, is 40% protein bound, and has an elimination half-life of 6 hours (range 2-12). Data from two placebo-controlled trials demonstrated the efficacy of ibutilide for converting AF or AFl of short duration (< or = 90 d) to normal sinus rhythm. A third placebo-controlled trial demonstrated efficacy in patients who developed AF or AFl following cardiac surgery. Comparative trials with procainamide and sotalol have shown at least similar and perhaps superior efficacy with ibutilide. There are no comparative trials with other antiarrhythmic drugs or with direct current cardioversion (DCC). In 586 clinical trial patients receiving ibutilide, the most significant adverse effect was the development of torsade de pointes in 25 patients (4.3%) including 10 cases (1.7%) in which the rhythm was sustained. All cases of torsade de pointes were terminated electrically and none resulted in death or severe morbidity. No prospective cost-effectiveness studies are available; however, results from two decision models suggest that ibutilide may have advantages over other drugs and first-line electrical cardioversion.
Ibutilide appears to be an effective alternative method for rapid conversion of recent-onset AF or AFl. The drug may be particularly useful in patients who have undergone recent cardiac surgery or those who are not ideal candidates for DCC. Although studies suggest that the risk of proarrhythmia and in particular torsade de pointes is relatively low, caution is advised until additional experience is gained in clinical practice.
探讨抗心律失常药物伊布利特在心房颤动（AF）或心房扑动（AFl）患者中的临床药理学。
利用MEDLINE检索（1983年1月至1997年12月）来识别有关伊布利特的相关英文文章。关键检索词包括伊布利特、AF、AFl、心脏复律和窦性心律。MEDLINE检索由综合综述文章和研究的参考文献进行补充。
选择描述伊布利特化学、药理学和药代动力学的研究及综述文章。对所有评估疗效和安全性的摘要及已发表的临床试验进行了综述。
总结了伊布利特药理学及作用机制的相关信息。数据从描述试验设计、患者群体、干预措施、评估方法、结果及统计学意义的临床试验中提取。
伊布利特是一种 Vaughan-Williams Ⅲ类抗心律失常药物，被批准静脉使用以快速终止近期发作的AF或AFl。该药物在肝脏中广泛代谢，分布容积为11 - 15L/kg，蛋白结合率为40%，消除半衰期为6小时（范围2 - 12小时）。两项安慰剂对照试验的数据表明伊布利特对将短病程（≤90天）的AF或AFl转为正常窦性心律有效。第三项安慰剂对照试验证明对心脏手术后发生AF或AFl的患者有效。与普鲁卡因胺和索他洛尔的比较试验表明伊布利特至少具有相似疗效，甚至可能更优。尚无与其他抗心律失常药物或直流电心脏复律（DCC）的比较试验。在586例接受伊布利特治疗的临床试验患者中，最显著的不良反应是25例（4.3%）发生尖端扭转型室速，其中10例（1.7%）为持续性节律。所有尖端扭转型室速病例均通过电复律终止，无一例导致死亡或严重并发症。尚无前瞻性成本效益研究；然而，两个决策模型的结果表明伊布利特可能比其他药物和一线电复律具有优势。
伊布利特似乎是快速转复近期发作的AF或AFl的有效替代方法。该药物在近期接受心脏手术的患者或那些不适合DCC的患者中可能特别有用。尽管研究表明促心律失常尤其是尖端扭转型室速的风险相对较低，但在临床实践中获得更多经验之前仍建议谨慎使用。
