Association of phosphatidylcholine and NSAIDs as a novel strategy to reduce gastrointestinal toxicity

Drugs of Today
L M LichtenbergerUpendra Marathi

Abstract

Nonsteroidal anti-inflammatory drugs (NSAIDs) are highly effective drugs that inhibit pain and inflammation, and perhaps due to the role of inflammation in the underlying etiology, NSAIDs have also demonstrated efficacy in reducing a patient's risk of developing a number of cancers and neurological diseases (e.g. Alzheimer's disease). The utility of these powerful drugs is limited due to their gastrointestinal (GI) side-effects, notably peptic ulceration and GI bleeding which is briefly reviewed here. We also describe the barrier property of the GI mucosa and how it is affected by NSAIDs, as it is our position that disruption of the surface barrier is an important component in the drugs' pathogenesis, in addition to selective inhibition of COX-2, which has proven to be problematic. We also discuss current alternative approaches being taken to mitigate the GI side-effects of NSAIDs, including developing combination drugs where NSAIDs are packaged with inhibitors of HCl secretion such as proton pump inhibitors or H2-receptor antagonists. We then present the rationale for the development of the PC associated NSAID technology which came out of our observation that the mammalian gastric mucosa has hydrophobic, nonwettable properties...Continue Reading

Citations

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