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 prophylactic treatment of acute coronary syndrome (ACS) comprising: administering, by inhalation, an effective amount of an aerosolized liquid pharmaceutical composition comprising argatroban to a subject in need thereof wherein the subject is suffering from acute coronary syndrome, wherein the effective amount is between about 0.1 and 150 mg/kg, and wherein at least about 5% of the pharmaceutical composition is delivered to the coronary arteries.
2. The method of claim 1 , wherein the subject is a human patient.
3. The method of claim 2 , wherein the patient is suffering from at least one condition selected from the group consisting of stable angina, unstable angina, myocardial infarction, valvular heart disease, stroke, and atrial fibrillation.
4. The method of claim 2 , wherein the patient has undergone heart transplant or a valve replacement in the heart.
5. The method of claim 2 , further comprising treating the patient with coronary artery bypass surgery or angioplasty.
6. The method of claim 1 , wherein the amount of the pharmaceutical composition peaks in the left atrium at a time ranging from 30 seconds to 180 minutes, 30 seconds to 90 minutes, 30 seconds to 60 minutes, or 30 seconds to 30 minutes after initiating the administration.
7. The method of claim 1 , wherein the effective amount of the pharmaceutical composition produces a ratio of factor Xa to factor IIa activity in the left atrium of at least 0.07.
8. The method of claim 1 , wherein the pharmaceutical composition is administered by an aerosolization device or a nebulizer.
9. The method of claim 8 , wherein the aerosolized liquid composition has a mass median aerodynamic diameter of less than 10 μm.
10. The method of claim 1 , wherein the pharmaceutical composition is self-administered by the subject.
11. The method of claim 2 , wherein the patient reaches an anticoagulated state in less than 30 minutes after initiating the administration of the pharmaceutical composition.
12. The method of claim 1 , wherein a dosage of 0.1 to 150 mg/kg the effective amount is at least 5 mg/kg.
13. The method of claim 1 , wherein 10% to 80% of the administered pharmaceutical composition reaches the left atrium.
14. The method of claim 1 , wherein the acute coronary syndrome comprises ischemic events, clotting, angina, myocardial infarction, or any combination thereof.
15. The method of claim 2 , wherein the subject is suffering from heparin-induced thrombocytopenia.
16. The method of claim 2 , wherein the subject has undergone percutaneous coronary intervention.
17. The method of claim 1 , wherein about 5% to 20% of the administered pharmaceutical composition reaches the coronary arteries.