Ibutilide (Corvert) is a structural analog of
sotalol and produces cardiac electrophysiological effects similar to those of
the antiarrhythmic agents in class III.
Ibutilide prolongs action
potential in isolated adult car-diac myocytes and increases both atrial and
ventricular refractoriness in vivo.
An additional action is blockade of outward potassium currents. Thus, ibutilide
acts by blocking the rapid component of the delayed rectifier current (IKr) as
well as by activation of a slow inward current carried predominantly by sodium.
Although there is evidence
that ibutilide causes a modest slowing of the sinus rate, there is no
significant change in heart rate.
Ibutilide causes an increase
in the atrial refractory period, an effect seen at rapid heart rates.
Ibutilide slows conduction
through the A-V node; however, there is no change in the PR interval on ECG.
Ibutilide increases the ERP
of ventricular myocytes and Purkinje fibers but has no clinically significant
ef-fect on QRS duration.
There are no changes in the
PR or QRS intervals, which reflects a lack of effect on the conduction
velocity. Although there is no relationship between the plasma concentration of
ibutilide and its antiarrhythmic effect, there is a dose-related prolongation
of the QT interval. The maximum effect on the QT interval is a function of both
the dose of ibutilide and the rate of infusion.
Ibutilide has no significant
effects on cardiac output, mean pulmonary arterial pressure, or pulmonary
capil-lary wedge pressure in patients with or without com-promised ventricular
characteristics of ibutilide are summarized next. The pharmacokinetics are
highly vari-able between patients. Because of extensive first-pass metabolism,
ibutilide is not suitable for oral administra-tion.
Oral bioavailability : >90%
Onset of action : Minutes
Peak response : Minutes
Plasma half-life : 3â€“4 hours
(range 2â€“12 hours)
Primary route of metabolism :
Primary route of excretion : Renal
concentration : Not applicable
Ibutilide is approved for the chemical cardioversion of
recent-onset atrial fibrillation and atrial flutter. Ibutilide appears to be more effective in terminating atrial flutter than
atrial fibrillation. It can also lower the defibrilla- tion threshold for
atrial fibrillation resistant to chemical cardioversion.
The major adverse effect
associated with the use of ibu-tilide is the risk of torsades de pointes due to
QT pro-longation. Other reported adverse cardiovascular events (all 2%) include
hypotension and hyperten-sion, bradycardia and tachycardia, and varying degrees
of A-V block. The incidence of noncardiac adverse events with the exception of
nausea does not differ from that of placebo.
Contraindications to the use
of ibutilide include base-line prolongation of the QT interval, use of other
QT-prolonging drugs, history of torsades de pointes, hyper-sensitivity to
ibutilide, uncorrected hypokalemia or hypomagnesemia, and pregnancy or
Ibutilide has significant