Azimilide dihydrochloride: a new class III anti-arrhythmic agent.
Azimilide dihydrochloride (Stedicor) is a new class III anti-arrhythmic agent that is being developed by Proctor & Gamble to treat supraventricular and ventricular arrhythmias. Development of this agent is being undertaken due to the high prevalence of atrial fibrillation and the lack of satisfactory therapy for this arrhythmia, along with the desire to develop therapy to reduce the risk of life-threatening ventricular arrhythmias in patients following myocardial infarction. The mechanism of action of azimilide is to block both the slowly conducting (I(Ks)) and rapidly conducting (I(Kr)) rectifier potassium currents in cardiac cells. This differs from other class III agents that block I(Kr) exclusively or in combination with sodium, calcium, or transient outward (I(to)) potassium current channels. Azimilide is distinguished by a relative lack of reverse use-dependence, excellent oral absorption, no need for dose titration, an option for out-patient initiation, no need for adjustment associated with renal or liver failure and a lack of interaction with warfarin or digoxin. It carries some risk of torsade de pointes and rarely, neutropoenia. Azimilide has shown dose-related efficacy in prolonging the time to recurrence of atrial fibrillation. A large trial examining the impact of azimilide on mortality in high-risk patients following myocardial infarction has completed enrolment and should yield data in the next couple of years and further studies are planned. Even if this trial fails to show a survival benefit, a neutral effect on mortality will make the agent attractive for atrial arrhythmias.
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University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75235-9047, USA.
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D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D001145:Arrhythmias, Cardiac / Q000188:drug therapy*; D002986:Clinical Trials as Topic; D006801:Humans; D006827:Hydantoins; D007093:Imidazoles / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D048289:Imidazolidines; D010879:Piperazines / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*
D000889:Anti-Arrhythmia Agents; D006827:Hydantoins; D007093:Imidazoles; D048289:Imidazolidines; D010879:Piperazines; C086123:azimilide