Relationship of nimesulide safety to its pharmacokinetics: assessment of adverse reactions.
Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most widely used drugs and their use is frequently associated with severe or even serious adverse events, which increase morbidity and mortality. The increase of toxic effects, primarily of the digestive system, due to treatment with NSAIDs, underlines a need for safer NSAIDs. Nimesulide (4-nitro-2-phenoxymethanesulphonanilide) is a chemically unique anti-inflammatory agent in that it has a higher pKa (6.5) than conventional acidic NSAIDs and it is one of the newer class of NSAIDs that are selective for cyclooxygenase-2. Nimesulide also has additional activities, among them effects on production/action of oxy-radicals and other components of neutrophil activation that may contribute to the spectrum of its anti-inflammatory activity as well as potentially reducing the likelihood of gastrointestinal ulcerogenicity. An analysis was performed of the safety data of nimesulide collected in clinical studies and from those reported spontaneously worldwide in the post-marketing phase. The results show that nimesulide is associated with a relatively low occurrence of adverse drug reactions especially in the gastrointestinal tract while those in the liver are within or below the general incidence with other NSAIDs.
Rainsford
K D
KD
Biomedical Research Centre, Sheffield Hallam University, UK.
D016907:Adverse Drug Reaction Reporting Systems; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects* / Q000493:pharmacokinetics*; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000009:adverse effects* / Q000493:pharmacokinetics*; D004064:Digestive System / Q000187:drug effects*; D004347:Drug Interactions; D006471:Gastrointestinal Hemorrhage / Q000139:chemically induced; D006801:Humans; D007527:Isoenzymes / Q000187:drug effects*; D008565:Membrane Proteins; D011451:Prostaglandin-Endoperoxide Synthases / Q000187:drug effects*; D013449:Sulfonamides / Q000009:adverse effects* / Q000493:pharmacokinetics*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; D013449:Sulfonamides; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; C012655:nimesulide