Uses of ion channel modulating compounds
Methods, formulations, dosing regimes, and routes of administration for the treatment or prevention of arrhythmias, including the treatment or prevention of atrial fibrillation. In these methods, the disease or condition is treated or prevented by administering one or more ion channel modulating compounds to a subject, where the ion channel modulating compound or compounds produce specific plasma levels in the subject. The ion channel modulating compounds may be cycloalkylamine ether compounds, particularly cyclohexylamine ether compounds.
1. A method for postponing onset of recurrence of arrhythmia in a human subject, the method comprising administering to the subject one or more doses of a formulation, wherein each dose of the formulation independently comprises an ion channel modulating compound of formula
including isolated enantiomeric, diastereomeric and geometric isomers thereof and mixtures thereof, or a pharmaceutically acceptable salt thereof;
wherein R 4 and R 5 are independently selected from hydrogen, hydroxy and C 1 -C 6 alkoxy; and
wherein the total concentration of the ion channel modulating compound in the blood plasma of the subject has a mean trough concentration of greater than about 1 ng/ml and/or a steady state concentration of greater than about 1 ng/ml.
2. The method of claim 1 , wherein the total concentration of the ion channel modulating compound in the blood plasma of the subject has a mean trough concentration of less than about 10 μg/ml and/or a steady state concentration of less than about 10 μg/ml.
3. The method of claim 1 , wherein the total concentration of the ion channel modulating compound in the blood plasma of the subject has a mean trough concentration of between about 0.3 μg/ml and about 3 μg/ml, and/or a steady state concentration between about 0.3 μg/ml and about 3 μg/ml.
4. The method of claim 1 , wherein the ion channel modulating compound is administered in two or more doses.
5. The method of claim 1 , wherein the doses are administered orally.
6. The method of claim 5 , wherein the formulation is a solid or liquid dosage form of the ion channel modulating compound.
7. The method of claim 1 , wherein the dose or doses are administered intravenously.
8. The method of claim 7 , wherein the formulation is an isotonic intravenous solution of the ion channel modulating compound.
9. The method of claim 1 , wherein each dose of the formulation comprises a monohydrochloride salt of the formula
10. The method of claim 1 , wherein the arrhythmia is an atrial arrhythmia.
11. The method of claim 10 , wherein the arrhythmia is an atrial fibrillation.