| abstract |
The present invention provides phospholipid prodrugs of aspirin, other salicylates, and nonsteroidal anti-inflammatory drugs useful in the therapy of chronic inflammatory disorders. The drugs are linked to either or both of the glycerol hydroxyls of a phospholipid or to available hydroxyls of phospholipid head groups by ester bonds. They may also be linked to available amines of phospholipid head groups by amine bonds. Drugs linked to phospholipid glycerol are released in vivo by the action of phospholipase A2 and other phospholipases, while those linked to the phospholipid head groups are released by other endogenous hydrolases. The phospholipid prodrugs reduce the gastrointestinal irritation and toxicity of these drugs when administered at high doses. The prodrugs further provide sustained serum levels of the drugs and allow longer intervals between doses through metabolically controlled release of the active agent. |