富马酸伊布利特中有机溶剂残留量的顶空毛细管GC测定

建立了顶空毛细管GC法同时测定富马酸伊布利特中甲醇、乙醇、二氯甲烷、丙酮、乙醚、四氢呋喃、吡啶7种有机溶剂的残留量。采用HP-1毛细管柱,FID检测器,水为溶剂。平均回收率分别为99.1%、98.9%、100.5%、97.9%、97.2%、98.6%、100.7%;RSD分别为1.84%、1.43%、1.66%、1.64%、1.99%、1.28%、3.52%。     

富马酸伊布利特与盐酸普罗帕酮治疗心房颤动和扑动的疗效比较

目的：比较静脉注射富马酸伊布利特与盐酸普罗帕酮治疗持续时间〈90d的房扑／房颤的有效性及安全性。方法：本研究为前瞻性随机单盲对照研究。房扑房颤患者共40例，随机分为试验组（伊布利特组，22例，其中房扑9例，房颤13例）和对照组（普罗帕酮组，18例，其中房扑7例。房颤11例）。两组分别在持续心电、血压监护下于10min内静脉推注伊布利特1mg或普罗帕酮70mg，如给药结束10min后仍未转复为窦性心律，重复前述治疗1次。观察给药后4h内的房扑／房颤的转复率及不良反应的发生情况。结果：40例中19例在90min内转复，其中盐酸普罗帕酮组5例，转复率27．8％，富马酸伊布利特组14例，转复率63．6％，两组比较差异有统计学意义（P〈0．05）。富马酸伊布利特组22例中有1例（4．4％）发生短阵室速，2例（8．1％）发生频发室早，未行特殊处理自行消失。无严重不良反应。结论：与普罗帕酮比较。富马酸伊布利特对房扑/房颤的转复具有明显的优势。     

Racemization of Ibutilide in Solution: A Factor to Consider When Choosing to Develop the Racemate or a Single Enantiomer

Pharmaceutical Research -     

伊布利特致尖端扭转性室性心动过速机制的研究

目的:探讨特效转复心房颤动药物伊布利特致尖端扭转性室性心动过速(Tdp)的机制。方法:利用兔左室楔形心肌块灌流伊布利特或溶有伊布利特的低钾低镁台氏液。30只新西兰大白兔随机分为正常组、伊布利特组和低钾低镁组,每组10只。正常组灌流台氏液,伊布利特组灌流2 mg/L伊布利特40 min,低钾低镁组灌流同浓度但溶于低钾低镁台氏液的伊布利特。同步记录各组内、外膜下心肌动作电位和容积心电图,观察灌流过程中早后除极(EAD)和Tdp的发生情况,对QT间期以及跨室壁复极离散度(TDR)的影响。结果:伊布利特组QT间期较正常组显著延长[(337±46)ms∶(548±73)ms],TDR也显著增加[(49±15)ms∶(132±36)ms],EAD的发生率为4/10,与正常组比较,均P<0.05;Tdp的发生率为0。低钾低镁组QT间期近一步延长至(652±184)ms、TDR增至(157±59)ms,EAD发生率为5/10,与正常组比较,均P<0.05,与伊布利特组比较,均P>0.05;Tdp的发生率增加为7/10,与正常组、伊布利特组比较,均P<0.05。结论:在伊布利特合并低钾低镁的情况下才易诱发Tdp,电解质正常时不...     

Conversion of Recent‐Onset Atrial Fibrillation or Flutter with Amiodarone after Ibutilide Has Failed: A Rapid,Efficient, and Safe Algorithm

Background: Ibutilide and amiodarone are used for the pharmacological conversion of atrial fibrillation (AF) or flutter (AFl), but their efficacy is rather moderate. Methods: To test whether the use of ibutilide as a first‐choice drug and of amiodarone as a second‐line treatment provides a rapid, effective, and safe algorithm for conversion of recent‐onset AF or AFl to sinus rhythm (SR), 85 consecutively recruited patients (59 women; mean age 69.7 ± 0.9 years) with AF or AFl of recent onset received 1 or 2 mg of ibutilide infusion. In the case of ibutilide failure, amiodarone was given (6 mg/kg IV infusion over 60 minutes followed by 1200 mg IV infusion over 24 hours) 4 hours later. Ten patients with AF or AFl of recent onset were used as controls. The maximum rate‐corrected QT interval was calculated in all patients and controls before the start of the study (baseline electrocardiogram (ECG)), 30 minutes later (30‐min ECG), and 4 hours later (4‐h ECG). Results: Fifty‐eight (68%) patients reversed to SR within the first 4 hours after the end of ibutilide infusion. In those 27 patients in whom ibutilide failed, amiodarone was given. Twenty‐four of them (28%) were converted to SR during amiodarone infusion. Therefore, in total, 82 (96%) patients with recent‐onset AF or AFl were converted to SR. The 10 controls were monitored for the same time period as the study patients and 5 (50%) out of them were spontaneously converted to SR (P < 0.0001). No pro‐arrhythmia or any other side effects were noticed in the study patients or in the controls. QTc was moderately decreased before the start of amiodarone infusion in patients group, while it did not differ among the three ECGs in controls. Conclusions: The combination of ibutilide as a first‐choice drug and of amiodarone infusion in the case of ibutilide failure provides an effective, rapid, and safe algorithm for restoration of SR in patients with AF or AFl of recent onset.     

Efficacy and safety of ibutilide for the conversion of monomorphic atrial tachycardia

BACKGROUND: Ibutilide is a class III antiarrhythmic drug, frequently used for conversion of atrial fibrillation and flutter. We studied the efficacy of ibutilide for acute conversion of monomorphic atrial tachycardia (monoAT) in a prospective, open label study in the intensive care unit of a cardiological clinic. METHODS: We examined 49 episodes of monoAT in 38 patients (19 men/19 women). Thirty-three patients (87%) suffered from structural heart disease. Twenty-three episodes occurred while on antiarrhythmic therapy with class I or III drugs. Patients with prolonged QT interval (except for patients with pretreatment with class III drugs), hypokalemia, left ventricular failure, and recent myocardial infarction were excluded. All patients received one or two doses of 1 mg ibutilide fumarate under continuous rhythm monitoring. RESULTS: Conversion to sinus rhythm occurred in 19 episodes (38.8%), in 6 episodes (12.2%) after the first dose. Conversion rate was significantly higher in patients with a short history of symptoms (66.6% vs 28.6%; P < 0.05), of documented arrhythmia (0.13 (0/5.7) vs 2.6 (0.38/23.5) months, median (interquartile range); P < 0.03), higher atrial rate (272 +/- 49 vs 207 +/- 36 beats/min (means +/- SD); P < 0.004), or without preexisting antiarrhythmic therapy (53.8% vs 21.7%; P < 0.02). No differences in conversion rates were found regarding gender, age, body mass index, left ventricular function, left atrial diameter, or underlying disease. In three episodes torsade de pointes occurred after ibutilide (6.1%), requiring defibrillation in two cases (4.1%). CONCLUSIONS: Ibutilide can be used for conversion of monoAT with a similar efficacy as for atrial fibrillation, but with a considerably lower efficacy compared to typical atrial flutter.     

静脉注射伊布利特转复心房扑动或心房颤动14例疗效分析

目的:比较伊布利特与胺碘酮转复心房扑动(AFL)或心房颤动(AF)的临床疗效。方法:将符合入选标准的27例AFL或AF患者随机分为伊布利特组14例,给予伊布利特注射液1 mg于10 min内静脉注射(静注);如无效10 min后再给予1 mg静注。胺碘酮组13例,给予胺碘酮注射液150 mg于15 min内静注;如无效10 min后再给予75 mg静注。观察转复为窦性心律的例数及时间。结果:伊布利特组转复为窦性心律的时间短于胺碘酮组(P0.05);伊布利特组与胺碘酮组分别有11例与6例在给药后0～30 min内转复为窦性心律;分别有3例与2例在给药后30～90 min内转复为窦性心律,总转复率分别为100.0%和61.54%。2组差异无统计学意义(P=0.167)。结论:伊布利特是一种快速、安全、有效的新型抗心律失常药物,为AFL或AF转复为窦性心律提供了新的选择。     

Frequency-Dependent Electrophysiological Effect of Ibutilide on Human Atrium and Ventricle

Most of the class III antiarrhythmic agents developed in recent years blocks the rapid component of delayed rectifier potassium current (IKr). IKr blocker shows reverse use-dependency and also may cause torsades de pointes at slower heart rate. Ibutilide fumarate, a novel class III antiarrhythmic agent, increases window Na(+) current at the action potential plateau phase. We studied the rate-dependent effect of ibutilide on the electrophysiological parameters of human atrium and ventricle. Franz catheter and a pacing catheter were placed closely in the high right atrium and right ventricular apex to record monophasic action potentials (MAP) during pacing at cycle length (PCL) of 600 ms and 350 ms in eight patients who underwent electrophysiological study. MAP duration of right atrium (RA-MAPD) and right ventricle (RV-MAPD), effective refractory period of RA and RV (RA-ERP and RV-ERP), intra-atrial conduction time (IACT) and intra-ventricular conduction time (IVCT) were measured before and after intravenous administration of ibutilide (0.01 mg/kg up to 1mg). A conduction time from RA pacing spike to distal coronary sinus potential was used to measure IACT, while QRS duration of surface ECG during RV pacing was used to measure IVCT. Ibutilide prolonged RA-MAPD by 60 ms at PCL 600 ms and by 53 ms at PCL 350 ms; RV-MAPD by 48 ms at PCL 600 ms and by 55 ms at PCL 350 ms. Ibutilide did not affected RA and RV-ERP/MAPD ratio, IACT, and IVCT. Ibutilide prolongs MAPD and ERP of human atrium and ventricle without reverse use-dependency.     

伊布利特联合胺碘酮转复持续性房颤的有效性及安全性研究

目的研究伊布利特联合胺碘酮对转复持续性房颤的有效性及安全性。方法选取持续性房颤的患者75例,随机分为研究组(n=39)和对照组(n=36),研究组序贯给予胺碘酮300 mg和伊布利特静脉注射,对照组给予与胺碘酮相同剂量的安慰剂(5%葡萄糖注射液)和伊布利特静脉注射。比较两组的转复率、室性心律失常发生率、f波间期、QT间期和QTc间期的变化。结果研究组与对照组比较,持续性房颤转复成功率为76.9%和58.3%;室性心律失常的发生率分别为1例(2.5%)和17例(47.2%)。结论 (1)静脉应用伊布利特联合胺碘酮对转复持续性房颤的成功率明显优于单独应用伊布利特,联合用药更具有明显的有效性;(2)明显降低了单用伊布利特时室性心律失常的发生率,联合用药提高转复安全性。