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| Formula | C27H31I2NO5 |
| Molar mass | 703.356 g·mol−1 |
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Budiodarone (ATI-2042) is anantiarrhythmic agent and chemical analog ofamiodarone that is currently being studied inclinical trials. Amiodarone is considered the most effective antiarrhythmic drug available,[1][2][3] but its adverse side effects, including hepatic, pulmonary and thyroid toxicity as well as multiple drug interactions,[4] are discouraging its use. Budiodarone only differs in structure from amiodarone through the presence of asec-butyl acetate side chain at position 2 of thebenzofuran moiety.[5] This side chain allows for budiodarone to have a shorterhalf-life in the body than amiodarone (7 hours versus 35–68 days) which allows it to have a faster onset of action and metabolism while still maintaining similar electrophysiological activity.[4] The faster metabolism of budiodarone allows for fewer adverse side effects than amiodarone principally due to decreased levels of toxicity in the body.
Arrhythmias may be caused by changes in ion channel mRNA and protein expression which modifyaction potential generation through dysfunctional channels and increase the likelihood of inappropriate electrical re-entry (electrical stimulus entering back into the cell to prematurely start the next action potential).[6] The increase in electrical re-entry causes thefibrillation or uncontrolled action potential discord ofatrial myocytes. Arrhythmias have historically been treated using atrialablation or antiarrhythmic drugs to decrease electrical re-entry and therefore fibrillation.
Budiodarone holds much promise as an antiarrhythmic drug to prevent fibrillation. As a drug that spans over many of antiarrhythmic drug classes, the electrophysiological activity of budiodarone includes:[4]
Through inhibiting potassium channels, budiodarone causes a decreased efflux of potassium out of the myocyte during therefractory period of its action potential, increasing the time it takes to reach the restingmembrane potential.
Through blocking sodium channels, budiodarone causes a decrease in sodium influx into myocytes during thedepolarization period of its action potential.
Through blocking calcium channels, budiodarone causes a decrease in calcium influx into myocytes, decreasing intracellular calcium and decreasing cardiaccontractility, which is beneficial in preventing arrhythmias, but detrimental in ventricular contraction.
Through prolonging the refractory and depolarization periods of the action potential, there is a decreased likelihood that electrical re-entry will occur.
Increasing the time interval between stimulus to atrium and/or atrium tobundle of his in action potential conduction slows the rate of myocyte contraction, thereby slowing heart rate.
Increasing the time interval of MAPD90 (response of monophasic action potential duration at 90% repolarization)in action potential conduction, slowing the rate of myocyte contraction, thereby slowing heart rate.
A decrease in heart rate reduces the risk of atrial fibrillation.
Preliminary trials of budiodarone have administered the drug orally as atartrate salt in amounts ranging from 200–800 mg bid.[7][8] Evidence has shown that 400–600 mgbid doses were associated with the highest reduction in atrial fibrillation burden (54.4% and 75% respectively)[8] while remaining free of the adverse side effects common with amiodarone.[7] In addition to reductions in atrial fibrillation burden, similar dose-dependent reductions in the number of atrial fibrillation episodes and the duration of atrial fibrillation episodes have been demonstrated.[7][8]
There has also been evidence of prolonged budiodarone cardiac effect days after drug discontinuation as the atrial fibrillation baseline measurements were not reached inwashout periods.[7] This suggests that budiodarone may promote atrial re-modelling to improve malfunctioning ion channels that once potentiated fibrillation.
Data on the effects of long-term budiodarone are not yet available. The completion of current clinical trials will examine chronic budiodarone use to confirm or deny its use as an effective and safe antiarrhythmic drug.