Harron D W, Brogden R N
Queen's University of Belfast.
Drugs. 1987 Dec;34(6):617-47. doi: 10.2165/00003495-198734060-00001.
Propafenone is a Class I antiarrhythmic agent with weak beta-adrenoceptor antagonist activity which can be given both intravenously and orally. Dosage must be individualised because of dose-dependent pharmacokinetics, a wide range of clinically effective plasma concentrations (64 to 3271 micrograms/L) after comparable doses, the presence of an active metabolite (5-hydroxy-propafenone) and genetically determined metabolic oxidation. In non-comparative studies propafenone 450 and 900 mg/day orally significantly suppressed premature ventricular complexes and couplets in 96% and 75% of patients, respectively, and abolished ventricular tachycardia in 75% of patients. Efficacy was confirmed in placebo-controlled studies in which propafenone 300 to 900mg daily suppressed premature ventricular complexes (greater than 80%) in 77% of patients; 87% of patients had significant reductions in couplets and abolition of ventricular tachycardia. In patients with ventricular arrhythmias refractory to other antiarrhythmic agents, propafenone 450 to 1200 mg/day suppressed arrhythmias in 63% of patients (in long term therapy 66%). Electrically induced arrhythmias were prevented by intravenously administered propafenone in 12 to 23% of patients. However, long term oral therapy was effective in 77% of patients selected using programmed electrical stimulation. Propafenone was also effective in suppressing atrial and AV nodal/junctional re-entrant tachycardias and Wolff-Parkinson-White tachycardias involving accessory pathways. A limited number of comparisons with other antiarrhythmic drugs indicate that the antiarrhythmic efficacy of propafenone is superior or similar to that of quinidine, disopyramide and tocainide, and comparable to that of lignocaine (lidocaine), flecainide and metoprolol against ventricular arrhythmias and a smaller number of atrial arrhythmias. Cardiovascular side effects indicate a proarrhythmic effect similar to that with other Class I drugs, occasional precipitation of congestive heart failure and conduction abnormalities; the latter two occur more often in patients with underlying ventricular dysfunction. Non-cardiovascular side effects (neurological, gastrointestinal) are well tolerated and generally resolve with continued therapy or dosage reduction. Thus, propafenone is an effective antiarrhythmic agent, and is a useful addition to currently available drugs, although further studies will be required to determine clearly its place in therapy compared with more established antiarrhythmic drugs.
普罗帕酮是一种Ⅰ类抗心律失常药物，具有较弱的β肾上腺素能受体拮抗活性，可静脉给药和口服给药。由于其剂量依赖性药代动力学、相当剂量后临床有效血药浓度范围较宽（64至3271微克/升）、存在活性代谢物（5-羟基普罗帕酮）以及遗传决定的代谢氧化作用，因此必须个体化给药。在非对照研究中，口服普罗帕酮450和900毫克/天分别使96%和75%的患者室性早搏和成对室性早搏明显减少，使75%的患者室性心动过速消失。在安慰剂对照研究中证实了其疗效，其中每日口服普罗帕酮300至900毫克使77%的患者室性早搏减少（大于80%）；87%的患者成对室性早搏显著减少且室性心动过速消失。在对其他抗心律失常药物难治的室性心律失常患者中，普罗帕酮450至1200毫克/天使63%的患者心律失常得到抑制（长期治疗时为66%）。静脉注射普罗帕酮可使12%至23%的患者预防电诱发的心律失常。然而，长期口服治疗对77%经程序电刺激筛选的患者有效。普罗帕酮在抑制房性和房室结/交界区折返性心动过速以及涉及旁路的预激综合征心动过速方面也有效。与其他抗心律失常药物进行的有限比较表明，普罗帕酮的抗心律失常疗效优于或类似于奎尼丁、丙吡胺和妥卡尼，在室性心律失常以及少数房性心律失常方面与利多卡因、氟卡尼和美托洛尔相当。心血管副作用表明其促心律失常作用与其他Ⅰ类药物相似，偶尔会诱发充血性心力衰竭和传导异常；后两者在有潜在心室功能障碍的患者中更常发生。非心血管副作用（神经、胃肠道）耐受性良好，通常在继续治疗或减少剂量后缓解。因此，普罗帕酮是一种有效的抗心律失常药物，是现有药物的有益补充，尽管还需要进一步研究以明确其与更成熟的抗心律失常药物相比在治疗中的地位。
