Unit aerosol doses for anticoagulation
Disclosed herein are methods for prophylactic treatment of acute coronary syndrome (ACS) comprising administering, by inhalation, an effective amount of a pharmaceutical composition comprising at least one anticoagulant or antiplatelet agent to a subject in need thereof, wherein the anticoagulant or antiplatelet agent first enters the heart via the left atrium.
1. A method for treatment of acute coronary syndrome and/or thrombosis comprising:
administering, by inhalation, an effective amount of a pharmaceutical composition to a subject in need thereof, wherein the pharmaceutical composition comprises (a) a univalent direct thrombin inhibitor selected from the group consisting of argatroban, melagatran, ximelagatran, and dabigatran,
wherein at least about 5% of the univalent direct thrombin inhibitor is delivered to the coronary arteries.
2. The method of claim 1 , wherein the pharmaceutical composition further comprises a direct factor Xa inhibitor.
3. The method of claim 1 , wherein the pharmaceutical composition is administered by a condensation aerosol, a liquid nebulizer, a nebulizer, an active dry powder inhaler, a passive dry powder inhaler, or a metered dose inhaler.
4. The method of claim 1 , wherein the pharmaceutical composition is in the form of an aerosol, a dry powder, or nebulized droplets.
5. The method of claim 1 , wherein the pharmaceutical composition has a mass median aerodynamic diameter of less than about 10 μm.
6. The method of claim 1 , wherein the pharmaceutical composition is self-administered by the patient.
7. The method of claim 1 , wherein the effective amount is administered in between about 1 and about 10 inhalations.
8. The method of claim 1 wherein the acute coronary syndrome comprises ischemic events, clotting, angina, myocardial infarction, or any combination thereof.
9. The method of claim 1 , wherein the effective amount is between about 0.1 and 150 mg/kg.
10. The method of claim 2 , wherein the direct factor Xa inhibitor is at least one of rivaroxaban, apixaban, edoxaban, betrixaban, darexaban, TAK-442 (letaxaban), eribaxaban, or otamixaban.
11. A method for prevention of acute coronary syndrome and/or thrombosis in a patient comprising:
inhaling an effective amount of a pharmaceutical composition, the pharmaceutical composition comprising an antithrombotic compound,
wherein the antithrombotic compound comprises (a) a univalent direct thrombin inhibitor selected from the group consisting of argatroban, melagatran, ximelagatran, and dabigatran,
wherein at least about 5% of the univalent direct thrombin inhibitor is delivered to the coronary arteries and/or wherein about 10% to about 80% of the antithrombotic compound is delivered to the left atrium.
12. The method of claim 11 , wherein the administration prevents platelet aggregation.
13. The method of claim 11 , wherein the patient is suffering from at least one of stable angina, unstable angina, myocardial infarction, valvular heart disease, stroke, and atrial fibrillation.
14. The method of claim 11 , wherein the patient is a heart transplant or heart valve replacement patient.
15. The method of claim 11 , wherein the pharmaceutical composition further comprises a pharmaceutically acceptable excipient.
16. The method of claim 11 , wherein the pharmaceutical composition is delivered at a therapeutic level to the heart and coronary arteries and at a sub-therapeutic level to rest of the body other than the heart and coronary arteries.
17. The method of claim 11 , wherein the pharmaceutical composition further comprises a direct factor Xa inhibitor.
18. The method of claim 17 , wherein the direct factor Xa inhibitor is at least one of rivaroxaban, apixaban, edoxaban, betrixaban, darexaban, TAK-442 (letaxaban), eribaxaban, or otamixaban.