Methods, compositions, and formulations for preventing or reducing adverse effects in a patient

Abstract

The present invention provides methods, compositions, formulations, and kits related to acadesine, or a prodrug, analog, or salt thereof, and/or a blood clotting inhibitor for preventing or reducing adverse side effects in a patient. The type of patient that may benefit includes a patient with decreased left ventricular function, a patient with a prior myocardial infarction, a patient undergoing non-vascular surgery, or a fetus during labor and delivery.

1 . A method of preventing or reducing adverse effects in a patient with decreased left ventricular function having an ejection fraction that is less than 30% comprising administering to said patient an effective amount of acadesine or a prodrug, analog, or salt thereof. 
     
     
         2 . The method of  claim 1  wherein the patient is female. 
     
     
         3 . The method of  claim 1  wherein the age of the patient is between about 65 years of age and about 95 years of age. 
     
     
         4 . A method of preventing or reducing adverse effects in a patient with a condition comprising administering to said patient an effective amount of acadesine or a prodrug, analog, or salt thereof, wherein said condition is selected from the group consisting of at least one prior myocardial infarction, at least two prior myocardial infarctions, at least three prior myocardial infarctions, and at least more than three prior myocardial infarctions. 
     
     
         5 . The method of  claim 4  wherein the most recent myocardial infarction occurred at a time selected from the group consisting of within the last 24 months, within the last 36 months, and within the last 48 months. 
     
     
         6 . The method of  claim 4  wherein the patient is female. 
     
     
         7 . The method of  claim 4  wherein the age of the patient is between about 65 years of age and about 95 years of age. 
     
     
         8 . A method of preventing or reducing adverse effects in a patient undergoing CABG surgery comprising a first step of administering to said patient an effective amount of acadesine, or a prodrug, analog, or salt thereof and a second step of administering to said patient an effective amount of a blood clotting inhibitor. 
     
     
         9 . The method of  claim 8 , wherein the administering of the blood clotting inhibitor occurs during the administering of the acadesine. 
     
     
         10 . The method of  claim 8 , wherein the acadesine is administered at a total dose of from 10 mg/kg to 200 mg/kg. 
     
     
         11 . The method of  claim 8 , wherein the blood clotting inhibitor is selected from the group consisting of an antiplatelet agent, thrombolytic enzyme, aggregation inhibitor, glycoprotein IIb/IIIa inhibitor, glycosaminoglycan, thrombin inhibitor, anticoagulant, heparin, low molecular weight heparin, coumarins, indandione derivatives and tissue plasminogen activator. 
     
     
         12 . The method of  claim 8 , wherein the blood clotting inhibitor is aspirin. 
     
     
         13 . The method of  claim 8 , wherein the acadesine is administered at 0.1 mg/kg/minute. 
     
     
         14 . The method of  claim 8 , wherein the acadesine is administered for a period of seven hours perioperatively. 
     
     
         15 . The method of  claim 8 , wherein the blood clotting factor is administered at a dosage of between 400 mg and 5 g. 
     
     
         16 . The method of  claim 8 , wherein the blood clotting factor is administered at least once within 48 hours after surgery. 
     
     
         17 . The method of  claim 8 , wherein the patient has a prior history of a condition selected from the group consisting of at least one myocardial infarction, at least two myocardial infarctions, at least three myocardial infarctions, and at least more than three myocardial infarctions. 
     
     
         18 . The method of  claim 17 , wherein the most recent myocardial infarction occurred at a time selected from the group consisting of within the last 24 months, within the last 36 months, and within the last 48 months. 
     
     
         19 . The method of  claim 2 , wherein the acadesine comprises 5-amino-1-β-D-(5-benzylamino-5-deoxy-1-β-D-ribofuranosyl)imidazole-4-carboxamide, 5-amino-1-(5-amino-5-deoxy-β-D-ribofuranosyl) imidazole-4-N-[(4-chlorophenyl)methyl]carboxamide, or prodrug, analog, or salt thereof. 
     
     
         20 . The method of  claim 8 , wherein the acadesine comprises 5-amino-1-β-D-(5-benzylamino-5-deoxy-1-β-D-ribofuranosyl)imidazole-4-carboxamide, 5-amino-1-(5-amino-5-deoxy-β-D-ribofuranosyl) imidazole-4-N-[(4-chlorophenyl)methyl]carboxamide, or prodrug, analog, or salt thereof.