INTRAVENOUS AMIODARONE - PHARMACOLOGY, PHARMACOKINETICS, AND CLINICALUSE

OBJECTIVES: To review the clinical pharmacology, pharmacokinetics, and clinical efficacy and safety of intravenous amiodarone. DATA IDENTIFI CATION: Articles were identified through a computer search of the Engl ish-language literature using MEDLINE (KR Information OnDisc) and the search term amiodarone. Additional articles were identified through ex amination of the bibliographies of the articles initially retrieved. S TUDY SELECTION: Relevant or representative animal studies, clinical tr ials, and case reports were selected for evaluation. Particular emphas is was placed on studies pertaining to the use of intravenous amiodaro ne in treatment-refractory ventricular fibrillation (VF) and hemodynam ically unstable ventricular tachycardia (VT). DATA EXTRACTION: The lit erature was assessed for adequate description of patients, study metho dologies (e.g., study design, number of patients), and outcomes. DATA SYNTHESIS: Amiodarone is an unusual class III antiarrhythmic that prod uces each of the four main types of antiarrhythmic action in addition to Other effects, such as vasodilatory, selective antithyroid, and oth er activities that may be therapeutically relevant. Amiodarone pharmac okinetics demonstrate extensive interpatient variability and are chara cterized by wide tissue distribution (steady-state volume of distribut ion 40-84 L/kg), slow total body clearance (90-158 mL/h/kg), long term inal elimination half-life (20-47 d), and extensive hepatic metabolism . The onset of maximal antiarrhythmic effect is a function of both ami odarone dosage and time. The high plasma concentrations achieved with intravenous dosing do not fully replicate the electrophysiologic effec ts observed following long-term oral administration, particularly with respect to class III activity. Available data suggest that intravenou s amiodarone is associated with an efficacy rate of 50% or more in tre atment-refractory VT/VF, and has a relatively rapid (2-24 h) onset of action. The drug is relatively well tolerated, but close hemodynamic, electrocardiographic, and hepatic function monitoring are required. Th e value of using amiodarone serum concentrations to guide therapy rema ins uncertain. CONCLUSIONS: Intravenous amiodarone is an effective, re latively safe antiarrhythmic for the treatment of recurrent, hemodynam ically unstable VT/VF refractory to other drug therapy in the acute ca re setting.