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.
Sodium N-(Methylsulfonyl)-N-(4-nitro-2-phenoxyphenyl)sulfamate : a water-soluble nimesulide prodrug for parenteral use / S. Rapposelli, M. Digiacomo, S. Franchi, S. Moretti, M. Pinza, P. Sacerdote, A. Balsamo. - In: MOLECULAR PHARMACEUTICS. - ISSN 1543-8384. - 7:5(2010), pp. 1871-1876.
Sodium N-(Methylsulfonyl)-N-(4-nitro-2-phenoxyphenyl)sulfamate : a water-soluble nimesulide prodrug for parenteral use
S. Franchi;P. SacerdotePenultimo
;
2010
Abstract
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.Pubblicazioni consigliate
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