Oral Amiodarone: Historical Overview and Development

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Abstract

Objectives.

To review the historical development of amiodarone and the changing perceptions of the drug, and discuss its electrophysiologic, pharmacologic, and pharmacokinetic properties.

Methods.

Review of relevant literature.

Results.

In the 1970s and 1980s a plethora of new antiarrhythmic agents, including amiodarone, was introduced. Amiodarone is predominately a class III antiarrhythmic, but also possesses class I, II, and IV effects. By 1977 it was described as the ideal antiarrhythmic agent. However, clinicians underestimated potential difficulties caused by misunderstanding its variable absorption, slow initial response at nonloading dosages, and extended half-life. Elevated dosages also produced frequent adverse effects. Thus, early enthusiasm for the drug's efficacy was gradually replaced by a focus on its toxicity. The 1990s witnessed reacceptance of the agent as more logical initial regimens and lower maintenance dosages decreased adverse effects, and amiodarone emerged as one of the few drugs effective in suppressing and preventing arrhythmias that does not increase mortality. Remaining challenges include delineation of an optimal oral regimen, identification of markers useful in clinical monitoring, and elucidation of the relationship between dose-tissue concentration and response and dosetoxicity associations.

Conclusion.

Amiodarone is an increasingly valuable component of today's antiarrhythmic therapy.

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