title: Sodium N-(methylsulfonyl)-N-(4-nitro-2-phenoxyphenyl)sulfamate: a water-soluble nimesulide prodrug for parenteral use.
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.
authors.affiliation: Dipartimento di Scienze Farmaceutiche, Università di Pisa, Via Bonanno 6, 56100 Pisa, Italy. simona.rapposelli@farm.unipi.it
authors.forename: Simona
authors.initials: S
authors.lastname: Rapposelli
authors.forename: Maria
authors.initials: M
authors.lastname: Digiacomo
authors.forename: Silvia
authors.initials: S
authors.lastname: Franchi
authors.forename: Sara
authors.initials: S
authors.lastname: Moretti
authors.forename: Mario
authors.initials: M
authors.lastname: Pinza
authors.forename: Paola
authors.initials: P
authors.lastname: Sacerdote
authors.forename: Aldo
authors.initials: A
authors.lastname: Balsamo
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics; D007249:Inflammation / Q000188:drug therapy; D007274:Injections, Intraperitoneal; D008297:Male; D011355:Prodrugs / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D013449:Sulfonamides / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D014867:Water
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D011355:Prodrugs; D013449:Sulfonamides; D014867:Water; C012655:nimesulide