Dronedarone
 | |
| Legal status | |
|---|---|
| Legal status | |
| Pharmacokinetic data | |
| Elimination half-life | 24 hours |
| Excretion | feces |
| Identifiers | |
| |
| CAS Number | |
| PubChem CID | |
| CompTox Dashboard (EPA) | |
| ECHA InfoCard | 100.109.411 |
| Chemical and physical data | |
| Formula | C31H44N2O5S |
| Molar mass | 556.758 g·mol−1 |
Dronedarone (also known as SR33589 or Multaq) is a drug under development by Sanofi-Aventis, mainly for the indication of cardiac arrhythmias (irregular heartbeat). It is currently in phase III trials for atrial fibrillation and in patients with an implantable cardioverter-defibrillator (ICD); a trial in heart failure was stopped as an interim analysis showed a possible increase in heart failure deaths.[2]
Chemistry
Chemically it is a benzofuran derivative related to amiodarone, a popular antiarrhythmic the use of which is limited to toxicity due its high iodine content (pulmonary fibrosis, thyroid disease) as well as by liver disease. Dronedarone lacks the iodine, and is expected to have less toxicity, yet it displays amiodarone-like class III antiarrhythmic activity in vitro[3] and in clinical trials.[2]
Pharmacokinetics
Dronedarone is less lipophilic than amiodarone, has a much smaller volume of distribution, and has an elimination half-life of 24 hours-- this stands in contrast to amiodarone's half-life of several weeks.[4] As a result of these pharmacokinetic characteristics, dronedarone dosing may be less complicated than amiodarone.
Clinical trials
In a 2007 trial in atrial fibrillation, dronedarone was significantly more effective than placebo in maintaining sinus rhythm, with no difference in lung and thyroid function in the short term.[5]
References
- ^ "FDA-sourced list of all drugs with black box warnings (Use Download Full Results and View Query links.)". nctr-crs.fda.gov. FDA. Retrieved 22 Oct 2023.
- ^ a b Køber L, Torp-Pedersen C, McMurray JJ; et al. (2008). "Increased mortality after dronedarone therapy for severe heart failure". N Engl J Med. 358 (25): 2678–87.
{{cite journal}}: Explicit use of et al. in:|author=(help); Unknown parameter|month=ignored (help)CS1 maint: multiple names: authors list (link) - ^ Sun W, Sarma JS, Singh BN (1999). "Electrophysiological effects of dronedarone (SR33589), a noniodinated benzofuran derivative, in the rabbit heart : comparison with amiodarone". Circulation. 100 (22): 2276–81. PMID 10578003.
{{cite journal}}: Unknown parameter|month=ignored (help)CS1 maint: multiple names: authors list (link) - ^ Dale KM, White CM (2007). "Dronedarone: an amiodarone analog for the treatment of atrial fibrillation and atrial flutter". Ann Pharmacother. 41 (4): 599–605. doi:10.1345/aph.1H524. PMID 17389667.
{{cite journal}}: Unknown parameter|month=ignored (help) - ^ Singh BN, Connolly SJ, Crijns HJ; et al. (2007). "Dronedarone for maintenance of sinus rhythm in atrial fibrillation or flutter". N Engl J Med. 357: 987–999. doi:10.1056/NEJMoa054686. PMID 17804843.
{{cite journal}}: Explicit use of et al. in:|author=(help); Unknown parameter|month=ignored (help)CS1 maint: multiple names: authors list (link)