Introduction

The historical development of the non-steroidal anti-inflammatory drugs (NSAIDs) has had several different phases. The use in the pre-nineteenth century period of various plant extracts for the treatment of pain classically culminated in the isolation and later synthesis, by Kolbe and Lautermann in 1874, of salicylic acid, probably the first synthetic NSAID 1, 2 . From this came the acetylated salicy-late, aspirin, supposedly safer and more effective than salicylic acid at the end of that...

B36

(a) hydroxylation of the phenoxy-ring in a position different than 4'. amine group with generation of the superoxide anion and ROS providing oxidative stress to cells. Other enzymes, involved in phase II reactions for nimesulide metabolism, are the N-acetyl-transferase (NAT), the uridine diphosphate glu-curonosyl-transferase (UGT) and sulphotransferase (ST). After administration of 14C nimesulide, the ratio between AUC values of the parent drug and total radioactivity in plasma ranged from...

Cox2human Sglddinptvllkerstel Cox2mouse Srlddinptvlikrrstel

Alignment 126 of mouse and human PGHS 1 and 2. Residue numbering follows the convention for the ram PGHS-1 structure (PDB entry 1prh). An asterisk under a given amino acid means identity in that position for mouse and human PGHS-2 enzymes the sign stands for a conserved residue in both PGHS-1 and PGHS-2 isozymes from the three species. The valine that occupies the same position as lle-523 in PGHS-1 and the arginine that replaces His-513 are labelled and highlighted in bold type. Chemical...

Info

A Paediatric patients (mean age 8.22 yrs) with hypoglycaemia. b On days 1 and 6, one administration from day 2 to 5, twice daily administration. c Creatinine plasma concentration < 1.2 mg dL. d Creatinine plasma concentration > 1.2 mg dL. e n 5. Symbols and abbreviations Cmax maximum plasma concentration tmax time to Cmax C12 drug concentration observed in plasma 12 h after administration AUC0_U and AUC area under the plasma concentration-time curve from 0 to 12h and to infinity t1 2,z...

Pharmacological Properties

Pharmacotherapeutic group ATC code M01AX17 Nimesulide is a non-steroidal anti-inflammatory drug with analgesic and antipyretic properties which acts as an inhibitor of prostaglandin synthesis enzyme cyclooxygenase. Nimesulide is well absorbed when given by mouth. After a single dose of 100 mg nimesulide a peak plasma level of 3-4 mg l is reached in adults after 2-3 h. AUC 20-35 mg h l. No statistically significant difference has been found between these figures and those seen after 100 mg given...

Nimesulide and neutrophil functional responses

While the inhibition of prostaglandin synthesis through the blockade of cyclooxy-genase is widely accepted as a mode of action of NSAIDs 39, 127 , during the last 3-4 decades, a variety of non-prostaglandin mediated effects of non-steroidal anti-inflammatory drugs have been reported 128-133 , suggesting that inhibition of cyclooxygenase does not represent the only explanation for the activity of these drugs. In this regard, neutrophils are considered a major potential target for NSAIDs because...

Novel nonpain uses of nimesulide

The uses of nimesulide in controlling pain, inflammation and fever are well known and are discussed in Chapter 5 and their adverse effects are discussed in Chapter 6 of this book. Here, some potentially novel applications of the drug are reviewed in preventing cancers, Alzheimer's disease, neurodegenerative and related dementias, immunodeficiency disorders, cataract formation and in some gynaecological conditions. Since the findings by Bennett et al. in 1975-1977 129-131 that cancerous tissues...

Versatile formulations

Nimesulide has been formulated into a wide range of pharmaceutical forms. However those registered and available in most of the countries worldwide are tablets, granules for oral suspension and suppositories. The pharmacokinetic and pharmaceutical properties of some of these are discussed in Chapters 2 and 3. Here, some aspects of the chemistry of these are discussed. Of particular interest are the attempts to develop formulations of nimesulide with the aim to enhance its absorption and...

Appendix A Trademark names for nimesulide

Helsinn trademark of original nimesulide worldwide (name of Helsinn's partners marketing authorization holders - & country) Aulin (Sulkaj Albania CSC Austria, Bosnia, Bulgaria, Czech Republic, Slovac Republic, Poland, Romania Serbia & Montenegro, Slovenia Schering Plough Chile, Ecuador, Philippines, Venezuela Gala Indonesia Helsinn Birex Therapeutics Ireland Roche Italy Ergo Maroc Morocco Angelini Portugal Vifor Switzerland), Mesulid (Sanofi-Aventis Latvia, Lithuania, Belarus, Hungary,...

Actions of nimesulide on cartilage degradation in vitro

Cartilage Degradation

When analysed in relation to the events involved in cartilage degradation in OA Figs 17-19 nimesulide has the potential to act on a considerable number of these with the potential to at least have no effects on the promotion of cartilage destruction and possibly to even prevent such changes. In the absence of any definitive evidence of preventative events of nimesulide in animal models of OA or Multifactorial actions of nimesulide on the pathways leading to oxyradical production, intracellular...

List of contributors

Bernareggi, Cell Therapeutics Inc., Europe, Via Ariosto 23, 20091 Bresso, Italy e-mail alberto.bernareggi ctimilano.com M. Bevilacqua, U O Endocrinologia e Diabetologia, Ospedale L Sacco-Polo Universitario, 20157 Milano, Italy e-mail m.bevilacqua hsacco.it mauriziobevilacqua fastwebnet.it M. Bianchi, Department of Pharmacology, Faculty of Medicine, University of Milan, Via Vanvitelli 32, 20129 Milano, Italy e-mail mauro.Bianchi unimi.it F. Bissoli, Clinica S Gaudenzio, Divisione Medicina,...

Physicochemical factors governing the oral bioavailability of nimesulide

The ability of nimesulide to cross the intestinal barrier was evaluated by the Ussing chamber 6 . This simple in vitro method is based on the assessment of the drug permeability through a portion of intact colon mucosa from the rabbit. The rate of drug penetration is parameterised through the apparent permeability coefficient, Papp, calculated according to the following equation Where dC dt concentration change in the receiver with time, V volume of the receiving chamber, A exposed tissue area,...

Nimesulide Actions and Uses

Birkh user Verlag Basel Boston Berlin K.D. Rainsford Biomedical Research Centre Sheffield Hallam University Howard Street Sheffield, S1 1WB UK A CIP catalogue record for this book is available from the Library of Congress, Washington D.C., USA Bibliographic information published by Die Deutsche Bibliothek Die Deutsche Bibliothek lists this publication in the Deutsche Nationalbibliografie detailed bibliographic data is available in the Internet at lt http dnb.ddb.de gt . ISBN 10 3-7643- 7068-8...

Discovery of R805 nimesulide

Sulphasalazine 1962

The development of nimesulide arose from investigations by Dr George GGI Moore a medicinal-organic chemist Fig. 2 , Dr Karl F Swingle a pharmacologist , Dr Bob RA Scherrer a medicinal chemist and their colleagues at Riker Laboratories Inc Northridge, California, US, later part of the 3M Company at St Paul, Minnesota, US . They had the idea that since the evidence in the late 1960s suggested that free radicals were important in chronic inflammatory diseases then drugs which scavenge these...