Several nimesulide preparations (i.e., tablet form, gels) have been marketed, but no parenteral solution has achieved the market because of their low wettability and unsatisfactory chemical-physical properties required for parenteral use. In this paper we describe the synthesis of the nimesulide prodrug 1 and its anti-inflammatory and antihyperalgesic properties. Pharmacological studies, carried out to evaluate the in vivo anti-inflammatory and analgesic activities of compound 1 and nimesulide, showed that sodium sulfamate 1 is an effective nimesulide prodrug that can be administered by parenteral route, undergoing a satisfactory absorption and an extensive transformation into the active nimesulide compound. Moreover, the evaluation of the plasma concentrations of nimesulide after rat treatment with compound 1 showed an increased and dose-dependent release of nimesulide. In contrast, the plasma concentrations of nimesulide, after "native" drug administration, still remain substantially unchanged. These preliminary results prompt further investigations on this prodrug as a possible candidate for parenteral use.
|Autori interni:||RAPPOSELLI, SIMONA|
|Autori:||RAPPOSELLI S; DIGIACOMO M; FRANCHI S; MORETTI S; PINZA M; SACERDOTE P; BALSAMO A|
|Titolo:||Sodium N-(Methylsulfonyl)-N-(4-nitro- 2-phenoxyphenyl)sulfamate: A Water-Soluble Nimesulide Prodrug for Parenteral Use|
|Anno del prodotto:||2010|
|Digital Object Identifier (DOI):||10.1021/mp1001137|
|Appare nelle tipologie:||1.1 Articolo in rivista|