Sulcardine administration for treatment of acute atrial fibrillation
Provided herein are compositions and methods for administration of sulcardine to a subject in need thereof.
1 . A method of causing a decrease in JTpc in a patient having cardiovascular disease, comprising administering to a patient a pharmaceutical composition comprising sulcardine or a pharmaceutically acceptable salt thereof, wherein the method causes a decrease in JTpc.
2 . The method of claim 1 , wherein the method causes a decrease in JTpc of no more than about 25 msec; or the method causes no change in TpTe.
3 . The method of claim 1 , wherein the method causes an increases in heart rate (HR) of no more than about 25%; or wherein the method further causes an increase in HR that is not clinically significant.
4 . The method of claim 1 , wherein the method inhibits early after depolarization.
5 . The method of claim 1 , wherein the method increases or decreases diastolic and/or systolic blood pressure by no more than about 25%.
6 . The method of claim 1 , wherein the method does not induce a 2nd or 3rd degree heart block.
7 . The method of claim 1 , wherein sulcardine, or a pharmaceutically acceptable salt thereof, is administered at a dose of 200 mg, 350 mg, 500 mg, or 600 mg.
8 . The method of claim 1 , wherein the pharmaceutically acceptable salt is an ethane-1,2-disulfonic acid salt of sulcardine.
9 . The method of claim 1 , wherein the QT and/or QRS intervals by about 5% to about 20% after the administration of the composition.
10 . The method of claim 1 , wherein the method causes a mean average plasma profile characterized by a Cmax after administering 200 mg of the compound, of at least about 1,500 ng/ml at about Tmax, and at most 25% of Cmax at about 1.0 hours after administration.
11 . The method of claim 1 , wherein the method further causes a mean average plasma profile characterized by a Cmax after administering 350 mg of the compound, of at least about 3,000 ng/ml at about Tmax, and at most 25% of Cmax at about 1.0 hours after administration.
12 . The method of claim 1 , wherein the method causes a mean average plasma profile characterized by a Cmax after administering 500 mg of the compound, of at least about 4,000 ng/ml at about Tmax, and at most 25% of Cmax at about 1.0 hours after administration.
13 . The method of claim 1 , wherein the method causes a mean plasma profile characterized by an average Cmax after administering 600 mg of the compound, of at least about 5,500 ng/ml at about Tmax, and at most 25% of Cmax at about 1.0 hours after administration.
14 . The method of claim 1 , wherein the method causes a decrease in plasma concentration of at least about 75% within about 1 hour after administration.
15 . The method of claim 1 , wherein the administration comprises intravenous injection, intramuscular injection, intraperitoneal injections, subcutaneous injection, or oral consumption.
16 . The method of claim 1 , wherein sulcardine, or a pharmaceutically acceptable salt thereof, is administered over a period less than about 1 hour.
17 . The method of claim 16 , wherein sulcardine, or a pharmaceutically acceptable salt thereof, is administered over a period of about 30 minutes.
18 . The method of claim 16 , wherein sulcardine, or a pharmaceutically acceptable salt thereof, is administered over a period of about 15 minutes.
19 . The method of claim 1 , wherein sulcardine, or a pharmaceutically acceptable salt thereof, is administered at a rate that does not produce an arrhythmia or a clinically significant change in heart rate or blood pressure.
20 . The method of claim 1 , wherein the treatment is for atrial flutter or wherein the AF is acute AF, paroxysmal AF or recurring AF.
21 . The method of claim 1 , wherein the method inhibits late sodium channels, fast sodium channels, L-type calcium channels in the heart, or a combination thereof, in the patient.
22 . The method of claim 1 , wherein a bimodal effect on QTc can occur including prolongation in QTc at lower drug exposure levels (doses) in association with INa cardiac ion channel inhibition followed by a potential plateauing or decrease in QTc interval at higher drug exposure levels (doses) associated with increasing inhibitory effect on NaL and ICa cardiac ion channels.
23 . A method of treating atrial fibrillation (AF) or atrial flutter in a patient suffering from cardiovascular disease, comprising administering to the patient 20 mg to 1000 mg of sulcardine, or a pharmaceutically acceptable salt thereof, wherein administering the sulcardine, or pharmaceutically acceptable salt thereof, to the patient causes a decrease in JTpc.