title: Pharmacological evaluation and preliminary pharmacokinetics studies of a new diclofenac prodrug without gastric ulceration effect.
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.
authors.affiliation: 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. santosjl@fcfar.unesp.br.
authors.forename: Jean Leandro Dos
authors.initials: JL
authors.lastname: Santos
authors.forename: Vanessa
authors.initials: V
authors.lastname: Moreira
authors.forename: Michel Leandro
authors.initials: ML
authors.lastname: Campos
authors.forename: Rafael Consolin
authors.initials: RC
authors.lastname: Chelucci
authors.forename: Karina Pereira
authors.initials: KP
authors.lastname: Barbieri
authors.forename: Pollyana Cristina Maggio
authors.initials: PC
authors.lastname: de Castro Souto
authors.forename: Márcio Hideki
authors.initials: MH
authors.lastname: Matsubara
authors.forename: Catarina
authors.initials: C
authors.lastname: Teixeira
authors.forename: Priscila Longhin
authors.initials: PL
authors.lastname: Bosquesi
authors.forename: Rosângela Gonçalves
authors.initials: RG
authors.lastname: Peccinini
authors.forename: Chung Man
authors.initials: CM
authors.lastname: Chin
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D002351:Carrageenan / Q000009:adverse effects; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D004008:Diclofenac / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D015232:Dinoprostone / Q000096:biosynthesis; D004195:Disease Models, Animal; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy; D007962:Leukocytes / Q000378:metabolism; D008297:Male; D051379:Mice; D015394:Molecular Structure; D010529:Peritoneal Cavity / Q000473:pathology; D011355:Prodrugs; D051381:Rats; D013276:Stomach Ulcer / Q000139:chemically induced
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D011355:Prodrugs; D004008:Diclofenac; D002351:Carrageenan; D051546:Cyclooxygenase 2; D015232:Dinoprostone; C473384:lumiracoxib