Pharmacological Evaluation and Preliminary Pharmacokinetics Studies of a New Diclofenac Prodrug without Gastric Ulceration Effect

Long-term nonsteroidal anti-inflammatory drugs (NSAIDs) therapy has been associated with several adverse effects such as gastric ulceration and cardiovascular events. Among the molecular modifications strategies, the prodrug approach is a useful tool to discover new safe NSAIDs. The 1-(2,6-dichlorop...

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Detalles Bibliográficos
Autores principales: dos Santos, Jean Leandro, Moreira, Vanessa, Campos, Michel Leandro, Chelucci, Rafael Consolin, Barbieri, Karina Pereira, de Castro Souto, Pollyana Cristina Maggio, Matsubara, Márcio Hideki, Teixeira, Catarina, Bosquesi, Priscila Longhin, Peccinini, Rosângela Gonçalves, Chin, Chung Man
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Molecular Diversity Preservation International (MDPI) 2012
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3509643/
https://www.ncbi.nlm.nih.gov/pubmed/23203127
http://dx.doi.org/10.3390/ijms131115305
Descripción
Sumario:Long-term nonsteroidal anti-inflammatory drugs (NSAIDs) therapy has been associated with several adverse effects such as gastric ulceration and cardiovascular events. Among the molecular modifications strategies, the prodrug approach is a useful tool to discover new safe NSAIDs. The 1-(2,6-dichlorophenyl)indolin-2-one is a diclofenac prodrug which demonstrated relevant anti-inflammatory properties without gastro ulceration effect. In addition, the prodrug decreases PGE(2) levels, COX-2 expression and cellular influx into peritoneal cavity induced by carrageenan treatment. Preliminary pharmacokinetic studies have shown in vivo bioconversion of prodrug to diclofenac. This prodrug is a new nonulcerogenic NSAID useful to treat inflammatory events by long-term therapy.

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