Pharmacological evaluation and preliminary pharmacokinetics studies of a new diclofenac prodrug without gastric ulceration effect

  • Int J Mol Sci. 2012 Nov 19;13(11):15305-20. doi: 10.3390/ijms131115305.
Jean Leandro Dos Santos  1 ,  Vanessa Moreira ,  Michel Leandro Campos ,  Rafael Consolin Chelucci ,  Karina Pereira Barbieri ,  Pollyana Cristina Maggio de Castro Souto ,  Márcio Hideki Matsubara ,  Catarina Teixeira ,  Priscila Longhin Bosquesi ,  Rosângela Gonçalves Peccinini ,  Chung Man Chin
Affiliations
  • 1. Lapdesf-Laboratory of Research and Drug Development, Drugs and Medicines Department, School of Pharmaceutical Science-UNESP Rodovia Araraquara Jaú Km. 01, 14801-902, Araraquara, SP, Brazil. [email protected].
PMID: 23203127 DOI: 10.3390/ijms131115305
Abstract

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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