Circulation. 1998;97:493-497
(Circulation. 1998;97:493-497.)
© 1998 American Heart Association, Inc.
Ibutilide
Katherine T. Murray, MD
From the Departments of Medicine and Pharmacology, Divisions of Clinical
Pharmacology and Cardiology, Vanderbilt University School of Medicine,
Nashville, Tenn.
Key Words: ibutilide • Cardiovascular Drugs • fibrillation • drugs
Ibutilide
is an antiarrhythmic drug that was recently marketed for the rapid
conversion of atrial fibrillation and atrial flutter. After
intravenous administration, ibutilide is moderately
effective in achieving prompt cardioversion to sinus rhythm, with
greater efficacy in patients who have atrial flutter. Like other drugs
that prolong ventricular repolarization, ibutilide
administration carries a risk of excessive QT prolongation, or the
acquired long-QT syndrome, with associated polymorphic
ventricular tachycardia (torsade de pointes),
necessitating careful patient selection and clinical monitoring during
drug administration.
Pharmacology
Ibutilide is a methanesulfonamide derivative with structural
similarities to the antiarrhythmic agent sotalol. This drug increases
action potential duration as its primary mechanism of action, so-called
class III effect, largely by blocking the rapid component of the
cardiac delayed rectifier potassium current,
IKr. In isolated cardiac myocytes,
ibutilide also prolongs action potential
duration,1 2 although its mechanism of action is
unique among available class III drugs. At nanomolar concentrations,
ibutilide appears to activate a slow inward current, largely
carried by sodium ions, that is unresponsive to
IKr blockers.1 2 3 In
addition, ibutilide blocks IKr on the basis
of both binding studies of 3H-dofetilide in
guinea pig ventricular myocytes4 and
patch-clamp studies in an atrial tumor cell line in which
IKr is the major repolarizing
current.5 Over a limited range of stimulation
rates, ibutilide can increase action potential duration without
significant reverse use dependence or loss of effect at rapid pacing
rates.6 7 In humans, ibutilide causes a dose- and
concentration-related increase in the uncorrected and rate-corrected QT
interval in both healthy . . . [Full Text of this Article]
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