Ibutilide

Ibutilide
Names
Trade namesCorvert
IUPAC name
  • N-(4-{4-[ethyl(heptyl)amino]-1-hydroxybutyl}phenyl)methanesulfonamide
Clinical data
Drug classClass III antiarrhythmic[1]
Main usesAtrial fibrillation, atrial flutter[1]
Side effectsPalpitations, low blood pressure, nausea, headache[1]
WHO AWaReUnlinkedWikibase error: ⧼unlinkedwikibase-error-statements-entity-not-set⧽
Pregnancy
category
  • C
Routes of
use		Intravenous
Typical dose1 gram[1]
External links
AHFS/Drugs.comMonograph
MedlinePlusa601248
Pharmacokinetics
BioavailabilityN/A
Protein binding40%
MetabolismLiver oxidation
Elimination half-life6 hours (2-12 hours)
ExcretionKidney (82%), fecal
Chemical and physical data
FormulaC20H36N2O3S
Molar mass384.58 g·mol−1
3D model (JSmol)
SMILES
  • O=S(=O)(Nc1ccc(cc1)C(O)CCCN(CC)CCCCCCC)C
InChI
  • InChI=1S/C20H36N2O3S/c1-4-6-7-8-9-16-22(5-2)17-10-11-20(23)18-12-14-19(15-13-18)21-26(3,24)25/h12-15,20-21,23H,4-11,16-17H2,1-3H3 checkY
  • Key:ALOBUEHUHMBRLE-UHFFFAOYSA-N checkY

Ibutilide, sold under the brand name Corvert, is a medication used to try to convert atrial fibrillation and atrial flutter of a recent onset.[1] It is given by gradual injection into a vein.[1]

Relatively common side effects include palpitations, low blood pressure, nausea, and headache.[1] Other side effects may include torsades de pointes and AV block.[1] Safety in pregnancy is unclear.[1] It is a class III antiarrhythmic and works by prolonging the action potential.[1][2]

Ibutilide was approved for medical use in the United States in 1995.[1] It is approved in part of Europe but not the United Kingdom.[3] In the United States it costs about 325 USD for a 1 mg dose as of 2021.[4]

Medical uses

Administration resulted in successful heart rhythm control in 31-44% of patients within 90 minutes, with sustained polymorphic ventricular tachycardia in 0.9-2.5% of patients. It appears to show better results in atrial flutter as compared to atrial fibrillation.[5]

Dosage

In those who weight more than 60 kg the typical dose is 1 mg while in those under 60 kg the dose is 10 mcg/kg.[1]

It is given by injection into a vein over 10 min.[1] Continuously ECG monitoring during the infusion and 4 hours after.[6]

Side effects

Like other antiarrhythmics, ibutilide can lead to abnormal heart rhythms due to its ability to prolong the QT interval, which can lead to the potentially fatal abnormal heart rhythm known as torsades de pointes. Consequently, the drug is contraindicated in patients that are likely to develop abnormal heart rhythms; this includes persons that have had polymorphic ventricular tachycardia in the past, have a long QT interval, sick sinus syndrome, or a recent myocardial infarction, among others.[7]

Mechanism of action

Ibutilide, like other class III antiarrhythmic drugs, blocks delayed rectified potassium current.[8]

It does have action on the slow sodium channel and promotes the influx of sodium through these slow channels.

Although potassium current seems to play a role, their interactions are complex and not well understood.[9] Ibutilide's unique mechanism works by an activation of a specific inward sodium current, thus producing its therapeutic response in which a prolonged action potential increases myocytes’ cardiac refractoriness in case of atrial fibrillation and flutter.

Pharmacokinetics

Absorption

Ibutilide is intravenously administered. It has a high first-pass metabolism, which results in a poor bioavailability when taken orally. Individual pharmacokinetic properties are highly viable during the clinical trial.[9][10]

Distribution

Ibutilide has a relatively large volume of distribution among individual subjects, which is about 11L/kg. Approximately 40% of the drug is bound with plasma albumin of healthy volunteers in a trial. This is also approximately close to patients with atrial fibrillation and flutter.[10]

Metabolism

Ibutilide has a high systemic plasma clearance that closes to the hepatic blood flow (29mL/min/kg). Its metabolic pathway is via liver's cytochrome P450 system by isoenzymes other than CYP3A4 and CYP2D6 by which the heptyl side chain of ibutilide is oxidized.[9][10] With eight metabolites are detected in the urine, however, only one is an active metabolite that shares the similar electrophysiologic property of the Class III antiarrhythmic agents.[9][10][11] The plasma concentration of this metabolite is only less than 10% of ibutilide.[10]

Excretion

After administration of ibutilide, it is quickly excreted by renal pathway with a half-life of approximately 6 hours. Approximately 82% of a 0.01 mg/kg dose is excreted in the urine during the trial. Among those, around 7% is excreted as unchanged drug. The remainder of the drug is excreted in feces (about 19%).[9]

See also

References

  1. 1 2 3 4 5 6 7 8 9 10 11 12 13 "Ibutilide Monograph for Professionals". Drugs.com. Archived from the original on 25 January 2021. Retrieved 24 November 2021.
  2. ↑ "DailyMed - CORVERT- ibutilide fumarate injection, solution". dailymed.nlm.nih.gov. Archived from the original on 11 December 2021. Retrieved 25 November 2021.
  3. ↑ "List of nationally authorised medicinal products Active substance: ibutilide" (PDF). Archived (PDF) from the original on 19 September 2020. Retrieved 25 November 2021.
  4. ↑ "Ibutilide Prices, Coupons & Patient Assistance Programs". Drugs.com. Retrieved 25 November 2021.
  5. ↑ Kowey PR, Stoenescu ML (2005). "Selection of drugs in pursuit of a rhythm control strategy". Progress in Cardiovascular Diseases. 48 (2): 139–45. doi:10.1016/j.pcad.2005.06.009. PMID 16253653.
  6. ↑ Lexi-Comp, Lexi-Drugs Online : Ibutilide.
  7. ↑ Jasek W, ed. (2007). Austria-Codex (in German). Vol. 1 (2007/2008 ed.). Vienna: Österreichischer Apothekerverlag. pp. 1768–71. ISBN 978-3-85200-181-4.{{cite book}}: CS1 maint: unrecognized language (link)
  8. ↑ Murray KT (February 1998). "Ibutilide". Circulation. 97 (5): 493–7. doi:10.1161/01.CIR.97.5.493. PMID 9490245.
  9. 1 2 3 4 5 Howard PA (January 1999). "Ibutilide: an antiarrhythmic agent for the treatment of atrial fibrillation or flutter". The Annals of Pharmacotherapy. 33 (1): 38–47. doi:10.1345/aph.18097. PMID 9972384.
  10. 1 2 3 4 5 Pharmacia-Upjohn, Corvert (ibutilide fumarate) injection package insert. July 2002: Kalamazoo, MI.
  11. ↑ Rogers KC, Wolfe DA (January 2001). "Ibutilide: a class III rapidly acting antidysrhythmic for atrial fibrillation or atrial flutter". The Journal of Emergency Medicine. 20 (1): 67–71. doi:10.1016/s0736-4679(00)00274-2. PMID 11165840.
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