Compositions and methods to prevent toxicity induced by nonsteroidal antiinflammatory drugs

Abstract

Nonsteroidal antiinflammatory drugs which have been substituted with a nitrogen monoxide group; compositions comprising (i) a nonsteroidal antiinflammatory drug, which can optionally be substituted with a nitrogen monoxide group and (ii) a compound that directly donates, transfers or releases a nitrogen monoxide group (preferably as a charged species, particularly nitrosonium); and methods of treatment of inflammation, pain, gastrointestinal lesions and/or fever using the compositions are disclosed. The compounds and compositions protect against the gastrointestinal, renal and other toxicities that are otherwise induced by nonsteroidal antiinflammatory drugs.

1 . A method for treating inflammation, pain, gastrointestinal lesions or fever in an animal in need thereof comprising administering to the animal a therapeutically effective amount of a composition comprising acetylsalicylic acid, or a pharmaceutically acceptable salt thereof, and isosorbide dinitrate. 
     
     
         2 . A method of reducing the gastrointestinal toxicity or renal toxicity of a nonsteroidal antiinflammatory drug in an animal in need thereof comprising administering to the animal a therapeutically effective amount of a composition comprising acetylsalicylic acid, or a pharmaceutically acceptable salt thereof, and isosorbide dinitrate, to the animal to reduce the gastrointestinal toxicity or renal toxicity of the nonsteroidal antiinflammatory drug. 
     
     
         3 . A method for accelerating gastrointestinal tissue repair in an animal in need thereof comprising administering to the animal a therapeutically effective amount of a composition comprising acetylsalicylic acid, or a pharmaceutically acceptable salt thereof, and isosorbide dinitrate. 
     
     
         4 . A method for treating inflammatory bowel disease, rheumatoid arthritis, osteoarthritis, thrombosis or Alzheimer's disease in an animal in need thereof comprising administering to the animal a therapeutically effective amount of a composition comprising acetylsalicylic acid, or a pharmaceutically acceptable salt thereof, and isosorbide dinitrate.