Advertisement

Clinical Pharmacokinetics

, Volume 35, Issue 4, pp 247–274 | Cite as

Clinical Pharmacokinetics of Nimesulide

  • Alberto BernareggiEmail author
Review Articles Drug Disposition

Abstract

Nimesulide is a selective COX-2 inhibitor used in a variety of inflammatory, pain and fever states. After healthy volunteers received oral nimesulide 100mg in tablet, granule or suspension form the drug was rapidly and extensively absorbed. Mean peak concentrations (Cmax) of 2.86 to 6.50 mg/L were achieved within 1.22 to 2.75 hours of administration. The presence of food did not reduce either the rate or extent of nimesulide absorption. When nimesulide was administered in the suppository form, the Cmax was lower and occurred later than after oral administration; the bioavailability of nimesulide via suppository ranged from 54 to 64%, relative to that of orally administered formulations.

Nimesulide is rapidly distributed and has an apparent volume of distribution ranging between 0.18 and 0.39 L/kg. It is extensively bound to albumin; the unbound fraction in plasma was 1%. The unbound fraction increased to 2 and 4% in patients with renal or hepatic insufficiency. With oral administration, the concentrations of nimesulide declined monoexponentially following Cmax. The estimated mean terminal elimination half-life varied from 1.80 to 4.73 hours. Excretion of the unchanged drug in urine and faeces is negligible.

Nimesulide is largely eliminated via metabolic transformation and the principal metabolite is the 4′-hydroxy derivative (M1). Minor metabolites have been detected in urine and faeces, mainly in a conjugated form. Pharmacological tests in vivo have shown that the metabolites are endowed with anti-inflammatory and analgesic properties, although their activity is lower than that of nimesulide.

Excretion in the urine and faeces accounted for 50.5 to 62.5% and 17.9 to 36.2% of an orally administered dose, respectively. The total plasma clearance of nimesulide, was 31.02 to 106.16 ml/h/kg, reflecting almost exclusive metabolic clearance. The drug has a low extraction ratio, close to 0.1. With twice daily oral or rectal administration of nimesulide, steady-state was achieved within 24 to 48 hours (2 to 4 administrations); only modest accumulation of nimesulide and M1 occurred.

Gender has only a limited influence on the pharmacokinetic profiles of nimesulide and M1. The pharmacokinetic profiles of nimesulide and M1 in children and the elderly did not differ from that of healthy young individuals. Hepatic insufficiency affected the pharmacokinetics of nimesulide and M1 to a significant extent: the rate of elimination of nimesulide and M1 was remarkably reduced in comparison to the rate of elimination in healthy individuals. Therefore, a dose reduction (4 to 5 times) is required in patients with hepatic impairment. The pharmacokinetic profile of nimesulide and M1 was not altered in patients with moderate renal failure and no dose adjustment in patients with creatinine clearances higher than 1.8 L/h is envisaged.

Pharmacokinetic interactions between nimesulide and other drugs given in combination [i.e. glibenclamide, cimetidine, antacids, furosemide (frusemide), theophylline, warfarin and digoxin] were absent, or of no apparent clinical relevance.

Keywords

Warfarin Adis International Limited Glibenclamide Nimesulide Rectal Administration 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Davis R, Brogden RN. Nimesulide: an update of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy. Drugs 1994; 48 (3): 431–54.PubMedCrossRefGoogle Scholar
  2. 2.
    Rabasseda X. Nimesulide: un farmaco antiinfiammatorio ehe inibisce selettivamente la cicloossigenasi 2. Drugs Today 1996; 32 Suppl. I/II: 1–24.Google Scholar
  3. 3.
    Famaey JP. In vitro and in vivo pharmacological evidence of selective cyclooxygenase-2 inhibition by nimesulide: an overview. Inflamm Res 1997; 46: 437–46.PubMedCrossRefGoogle Scholar
  4. 4.
    Rabasseda X. Safety profile of nimesulide: ten years of clinical experience. Drugs Today 1997; 33 (1): 41–50.CrossRefGoogle Scholar
  5. 5.
    Taniguchi Y, Ikesue A, Yopkoyama K, et al. Selective inhibition by nimesulide, a novel non-steroidal anti-inflammatory drug, with prostaglandin endoperoxide synthase-2 activity in-vitro. Pharm Sci 1995; 1: 173–5.Google Scholar
  6. 6.
    Tavares IA, Bishai PM, Bennett A. Activity of nimesulide on constitutive and inducible cyclooxygenase. Arzneimforsch Drug Res 1995; 45: 1–3.Google Scholar
  7. 7.
    Patrignani P, Panara MR, Sciulli MG, et al. Differential inhibition of human prostaglandin endoperoxide synthase-1 and -2 by nonsteroidal anti-inflammatory drugs. J Physiol Pharmacol 1997; 48 (4): 623–31.PubMedGoogle Scholar
  8. 8.
    Patrignani P, Panara MR, Santini G, et al. Differential inhibition of the cyclooxygenase activity of prostaglandin endoperoxide synthase isozymes in vitro and ex vivo. 10th InternationalConference on Prostaglandins and Related Compounds [abstract]. 1996 Sept 22–27; Vienna; 115.Google Scholar
  9. 9.
    Vago T, Bevilacqua M, Norbiato G. Effect of nimesulide action time dependence on selectivity towards prostaglandin G/H synthase/cyclooxygenase activity. Arzneimforsch Drug Res 1995; 45: 4–6.Google Scholar
  10. 10.
    Bianco S, Robuschi M, Gambaro G, et al. Bronchial inflammation and NSAIDs. Drug Invest 1991; 3 Suppl. 2: 33–8.CrossRefGoogle Scholar
  11. 11.
    Tofanetti O, Casciarri I, Cipolla PV, et al. Effect of nimesulide on cyclo-oxygenase activity in rats’ gastric mucosa and inflammatory exudate. Med Sci Res 1989; 17: 745.Google Scholar
  12. 12.
    Cipollini F, Mecozzi V, Altilia F. Endoscopic assessment of the effects of nimesulide in the gastric mucosa: comparison with indomethacin. Curr Ther Res 1989; 45: 1042–8.Google Scholar
  13. 13.
    Grossman CJ, Wiseman J, Lucas FS, et al. Inhibition of constitutive and inducible cyclo-oxygenase activity in human platelets and mononuclear cells by NSAIDs and COX 2 inhibitors. Inflamm Res 1995; 44: 253–7.PubMedCrossRefGoogle Scholar
  14. 14.
    Vane JR, Botting RM. Overview: mechanisms of action of antiinflammatory drugs. In: Vane JR, Botting J, Botting R, editors. Improved non-steroid anti-inflammatory drugs. COX-2 Enzyme Inhibitors. Amsterdam: Kluwer Academic Publishers/William Harvey Press, 1996: 1–27.CrossRefGoogle Scholar
  15. 15.
    Bevilacqua M, Vago T, Baldi G, et al. Nimesulide decreases Superoxide production by inhibiting phosphodiesterase type IV. Eur J Pharmacol 1994; 268: 415–23.PubMedCrossRefGoogle Scholar
  16. 16.
    Bevilacqua M, Vago T, Beretta A. Nimesulide as inhibitor of Superoxide anions (O2-) production by human polymorphonuclear leukocytes. Pain Reproduct 1988; 31: 265–72.Google Scholar
  17. 17.
    Capecchi PL, Ceccatelli L, Beermann U, et al. Inhibition of neutrophil function in vitro by nimesulide. Preliminary evidence of an adenosine-mediated mechanism. Arzneimittel forschung 1993; 43: 992–6.PubMedGoogle Scholar
  18. 18.
    Capsoni F, Venegoni E, Minonzio F, et al. Inhibition of neutrophil oxidative metabolism by nimesulide. Agents Actions 1987; 21: 121–9.PubMedCrossRefGoogle Scholar
  19. 19.
    Dallegri F, Dapino P, Ottonello L, et al. Suppression of neutrophil chloramine production by nimesulide: a possible contribution to the anti-inflammatory activity of the drug. Drug Invest 1991; 3 Suppl. 2: 75–8.CrossRefGoogle Scholar
  20. 20.
    Ottonello L, Dapino P, Pastorino G, et al. Nimesulide as a downregulator of the activity of neutrophil myeloperoxidase pathway: focus on the histoprotective potential of the drug during inflammatory processes. Drugs 1993; 46 Suppl. 1: 29–33.PubMedCrossRefGoogle Scholar
  21. 21.
    Ottonello L, Dapino P, Dallegri F. Inactivation of α-1 proteinase inhibitor by neutrophil metalloproteinases: crucial role of the myeloperoxidase system and effects of the anti-inflammatory drug nimesulide. Respiration 1993; 60: 32–7.PubMedCrossRefGoogle Scholar
  22. 22.
    Ottonello L, Dapino P, Scirocco MC, et al. Sulphonamides as anti-inflammatory agents: old drugs for new therapeutic strategies in neutrophilic inflammation? Clin Sci 1988; 88: 331–6.Google Scholar
  23. 23.
    Dallegri F, Ottonello L, Dapino P, et al. Effect of nonsteroidal anti-inflammatory drugs on the neutrophil promoted inactivation of α-1-proteinase inhibitor. J Rheumatol 1992; 19: 419–23.PubMedGoogle Scholar
  24. 24.
    Dallegri F, Ottonello L, Dapino P, et al. The anti-inflammatory drug nimesulide rescues α- 1-proteinase inhibitor from oxidative inactivation by phagocytosing neutrophils. Respiration 1992; 59: 1–4.PubMedCrossRefGoogle Scholar
  25. 25.
    Dallegri F, Patrone F, Ballestrero A, et al. Inactivation of neutrophil-derived hypochlorous acid by nimesulide: a potential mechanism for the tissue protection during inflammation. Int J Tissue React 1990; 12 (2): 107–11.PubMedGoogle Scholar
  26. 26.
    Dallegri F, Ottonello L, Gatti F, et al. Neutrophil oxidative responses. Cell-directed and scavenging actions of the anti-inflammatory drug nimesulide. Drug Invest 1991; 3 Suppl. 2: 71–4.CrossRefGoogle Scholar
  27. 27.
    Berti F, Rossoni G, Buschi A, et al. Antianaphylactic and antihistamine activity of the nonsteroidal anti-inflammatory compound nimesulide in guinea-pig. Arzneimittel forschung 1990; 40: 1011–6.PubMedGoogle Scholar
  28. 28.
    Casolaro V, Meliota S, Marino O, et al. Nimesulide, a sulfonanilide nonsteroidal anti-inflammatory drug, inhibits mediator release from human basophils and mast cells. J Pharmacol Exp Ther 1994; 276: 1375–85.Google Scholar
  29. 29.
    Verhoeven AJ, Tool ATJ, Kuijpers TW, et al. Nimesulide inhibits platelet-activating factor synthesis in activated human neutrophils. Drugs 1993; 46 Suppl. 1: 52–8.PubMedCrossRefGoogle Scholar
  30. 30.
    Pelletier JP, Martel-Pelletier J. Effects of nimesulide and naproxen on the degradation and metalloprotease synthesis of human osteoarthritic cartilage. Drugs 1993; 46 Suppl. 1: 34–9.PubMedCrossRefGoogle Scholar
  31. 31.
    Bernareggi A. The pharmacokinetic profile of nimesulide in healthy volunteers. Drugs 1993; 46 Suppl. 1: 64–72.PubMedCrossRefGoogle Scholar
  32. 32.
    Olive G, Rey E. Effect of age and disease on the pharmacokinetics of nimesulide. Drugs 1993; 46 Suppl. 1: 73–8.PubMedCrossRefGoogle Scholar
  33. 33.
    Castoldi D, Monzani V, Tofanetti O. Simultaneous determination of nimesulide and hydroxynimesulide in human plasma and urine by high-performance liquid chromatography. J Chromat B 1988; 425: 413–8.CrossRefGoogle Scholar
  34. 34.
    Bernareggi A, Castoldi D, Nava ML, et al. Linear pharmacokinetics of oral nimesulide in healthy male volunteers treated with 25, 50 and 100mg [Internal Report 02/PKB/98]. Boehringer Mannheim Italia, 1998. (Data on file).Google Scholar
  35. 35.
    Remuzzi G, Gaspari F, Taiocchi L. Development of micromethods to study the pharmacokinetic profile for brodimoprim and nimesulide in small volumes of biological fluids. Helsinn Healthcare, 1991. (Data on file).Google Scholar
  36. 36.
    Abbiati G, Rigoldi M, Parisi S, et al. Farmacocinetica e biodisponibilità di nimesulide β-ciclodestrina granulate nel volontario sano. Giorn Ital Ric Clin Terap 1996; 17: 1–4.Google Scholar
  37. 37.
    Pandya KK, Satia MC, Modi IA, et al. High-performance thinlayer chromatography for the determination of nimesulide in human plasma, and its use in pharmacokinetic studies. J Pharm Pharmacol 1997; 49: 773–6.PubMedCrossRefGoogle Scholar
  38. 38.
    Giachetti C, Tenconi A. Determination of nimesulide and hydroxynimesulide in human plasma by high performance liquid chromatography. Biomed Chromatogr 1998; 12: 50–6.PubMedCrossRefGoogle Scholar
  39. 39.
    Lücker PW. Study on the pharmacokinetics (food/drug interaction) and relative bioavailability of three different treatments with nimesulide in 18 healthy male volunteers [TSD No. 5565E]. Helsinn Healthcare. 1992. (Data on file).Google Scholar
  40. 40.
    Lücker PW. Report on the pharmacokinetics and relative bioavailability/bioequivalence of three different nimesulide formulations in 18 healthy male volunteers [TSD No. 5356E]. Helsinn Healthcare, 1991. (Data on file).Google Scholar
  41. 41.
    Alessandrini A, Ballarin E, Bastianon A, et al. Confronto di biodisponibilità tra due diverse forme farmaceutiche orali equidosate di nimesulide in volontari sani. Clin Ter 1986; 118: 177–82.PubMedGoogle Scholar
  42. 42.
    Scheen A. Open, randomized, crossover, bioequivalence study of three different formulations of nimesulide, after single oral dose administration in 24 healthy subjects [TSD No. 7215E]. Helsinn Healthcare, 1997. (Data on file).Google Scholar
  43. 43.
    Lücker PW Report of the study on the pharmacokinetics of nimesulide and its main metabolite 4-OH-nimesulide after oral administration of three different doses in healthy male volunteers [TSD No. 5781E]. Helsinn Healthcare, 1993. (Data on file).Google Scholar
  44. 44.
    De Caro G. Studio comparativo di farmacocinetica e biodisponibilità nell’uomo su formulazioni a base di nimesul-ide per uso orale (cpr 100mg) e rettale (supposte da 200mg) delle ditte LPB (Mesulid®) e BBR (Aulin®) in somministrazione singola e ripetuta [TSD No. 5437E]. Helsinn Healthcare, 1989. (Data on file).Google Scholar
  45. 45.
    Bernasconi PC. Pharmacokinetics of nimesulide: relative bioavailability of the rectal versus the oral administration. As ingle and repeated dose study in healthy volunteers [TSD No. 5252E]. Helsinn Healthcare, 1989. (Data on file)).Google Scholar
  46. 46.
    Gandini R, Montalto C, Castoldi D, et al. First dose and steadystate pharmacokinetics of nimesulide and its 4-hydroxy metabolite in healthy volunteers. Farmaco 1991; 46: 1061–79.Google Scholar
  47. 47.
    Ugazio AG, Guarnaccia S, Berardi M, et al. Clinical and pharmacokinetic study of nimesulide in children. Drugs 1993; 46 Suppl. 1: 215–8.PubMedCrossRefGoogle Scholar
  48. 48.
    Pulkkinen M. Nimesulide in dysmenorrhoea. Drugs 1993; 46 Suppl. 1: 129–33.PubMedCrossRefGoogle Scholar
  49. 49.
    Diamond G. Standard dossier. Vol 2. Single dose study using R805-14C [TSD No. 3007E]. Helsinn Healthcare, 1976: 181–210. (Data on file).Google Scholar
  50. 50.
    Allemon AM, Lebacq E. Study of the excretion balance and metabolism of [14C]nimesulide after single oral dose administration in 6 healthy male volunteers [TSD No. 5755E]. Helsinn Healthcare, 1993. (Data on file).Google Scholar
  51. 51.
    McCracken NW, Sanderson BJ, Young CG. The excretion and plasma kinetics of [14C]nimesulide in man following a single oral administration [TSD No. 7277E]. Helsinn Healthcare, 1997. (Data on file).Google Scholar
  52. 52.
    Brambilla A, Maffei Facino R. Metabolismo del farmaco antiinfiammatorio nimesulide nell’uomo [thesis]. Milan: Faculty of Pharmacy, University of Milan, 1989.Google Scholar
  53. 53.
    Maffei Facino R, Carini M, Stefani R, et al. In vitro metabolism of the antiinflammatory drug nimesulide in man: simultaneous determination of the main urinary metabolites by HPLC with UV-DAD detection. Proceedings of the 7th Meeting on Recent Developments in Pharmaceutical Analysis (RDPA ‘97); 1997 Sep 16–22; Isola d’Elba, 28.Google Scholar
  54. 54.
    Castoldi D. Escrezione urinaria della nimesulide dopo somministrazione unica al volontario sano [INternal report]. Boehringer Mannheim Italia, 1989. (Data on file).Google Scholar
  55. 55.
    Casciarri I, Bernareggi A. Disposition of total radioactivity and plasma levels of nimesulide and OH-nimesulide in rats after intravenous and oral administration [Report No. 2/PK/91]. Boehringer Mannheim Italia. 1991. (Data on file).Google Scholar
  56. 56.
    Lin JH, Cocchetto DM, Duggan DE. Protein binding as a primary determinant of the clinical pharmacokinetic properties of non-steroidal anti-inflammatory drugs. Clin Pharmacokinet 1987; 12: 402–32.PubMedCrossRefGoogle Scholar
  57. 57.
    Verbeeck RK. Pharmacokinetic drug interactions with nonsteroidal anti-inflammatory drugs. Clin Pharmacokinet 1990; 19 (1): 44–66.PubMedCrossRefGoogle Scholar
  58. 58.
    Brouwers J, de Smet P. Pharmacokinetic-pharmacodynamic drug interactions with nonsteroidal anti-inflammatory drugs. Clin Pharmacokinet 1994; 27 (6): 462–85.PubMedCrossRefGoogle Scholar
  59. 59.
    Graham GG, Champion GD, Day RO, et al. Patterns of plasma concentrations and urinary excretion of salicylate in rheumatoid arthritis. Clin Pharmacol Ther 1977; 22: 410–20.PubMedGoogle Scholar
  60. 60.
    Davies NM, Anderson KE. Clinical pharmacokinetics of diclofenac. Clin Pharmacokinet 1997; 33 (3): 184–213.PubMedCrossRefGoogle Scholar
  61. 61.
    Davies NM. Clinical pharmacokinetics of flurbiprofen and its enantiomers. Clin Pharmacokinet 1995; 28 (2): 100–14.PubMedCrossRefGoogle Scholar
  62. 62.
    Davies NM. Clinical pharmacokinetics of tiaprofenic acid and its enantiomers. Clin Pharmacokinet 1996; 31 (5): 331–47.PubMedCrossRefGoogle Scholar
  63. 63.
    Davies NM, Anderson KE. Clinical pharmacokinetics of naproxen. Clin Pharmacokinet 1997; 32 (4): 268–93.PubMedCrossRefGoogle Scholar
  64. 64.
    Pulkkinen MO, Vuento M, Macciocchi A, et al. Distribution of oral nimesulide in female genital tissues. Biopharm Drug Disp 1991; 12: 113–7.CrossRefGoogle Scholar
  65. 65.
    Lignière GC, Tamborini U, Panarace G, et al. La nimesulide nel liquido sinoviale di paziente con artrite reumatoide. Farmaci Terapia 1990; 7 (3): 173–6.Google Scholar
  66. 66.
    Vilageliu J. Nimesulide: evaluation of protein binding and the effects of possible displacers [TSD No. 3545E]. Helsinn Healthcare, 1983. (Data on file).Google Scholar
  67. 67.
    Bree F, Nguyen P, Urien S, et al. Nimesulide binding to components within blood. Drugs 1993; 46 Suppl. 1: 83–90.PubMedCrossRefGoogle Scholar
  68. 68.
    Milvio 1984. Confronto di biodisponibilità tra due diversi lotti con massa witepsol [TSD No. 4038.1.I]. Helsinn Healthcare, 1984. (Data on file).Google Scholar
  69. 69.
    Maffei Facino R, Carini M, Brambilla A, et al. Metabolism of nimesulide in man and radical scavenging activity of its main metabolites [abstract]. 3rd Interscience World Conference on Antirheumatics, Analgesics, Immunomodulators; 1989 Mar 15–18; Monte Carlo, 244.Google Scholar
  70. 70.
    Maffei Facino R, Carini M, Aldini G. Antioxidant activity of nimesulide and its main metabolites. Drugs 1993; 46 Suppl. 1: 15–21.CrossRefGoogle Scholar
  71. 71.
    PirovanoR. Study of the capacity of the test article BBR2335/7 to induce gene mutations in strains of Salmonella typhimurium [RBM Exp. No. 880312]. Boehringer Mannheim Italia, 1988. (Data on file).Google Scholar
  72. 72.
    Pirovano R. Study of the capacity of the test article BBR 2395 to induce gene mutations in strains of Salmonella typhimurium [RBM Exp. No. 890685]. Boehringer Mannheim Italia, 1989. (Data on file).Google Scholar
  73. 73.
    Brodie B, Lowman E, Burns J, et al. Observations on the antirheumatic and physiologic effects of phenylbutazone and some comparisons with cortisone. Am J Med 1954; 16: 181–90.PubMedCrossRefGoogle Scholar
  74. 74.
    Runkel R, Forchielli E, Sevelius H, et al. Nonlinear plasma level response to high doses of naproxen. Clin Pharmacol Ther 1974; 15: 261–6.PubMedGoogle Scholar
  75. 75.
    Lin JH, Hooke KF, Yeh KC, et al. Dose-dependent pharmacokinetics of diflunisal in rats: dual effects of protein binding and metabolism. J Pharmacol Exp Ther 1985; 235: 402–6.PubMedGoogle Scholar
  76. 76.
    Schärli AF, Brülhart K, Monti T. Pharmacokinetics and therapeutic study with nimesulide suppositories in children with post-operative pain and inflammation. J Int Med Res 1990; 18: 315–21.PubMedGoogle Scholar
  77. 77.
    Gupta SK, Prakash J, Awor L, et al. Anti-inflammatory activity of topical nimesulide gel in various experimental models. Inflamm Res 1996; 45: 590–2.PubMedCrossRefGoogle Scholar
  78. 78.
    Inveresk Clinical Research International. Acomparative kinetic study of nimesulide following administration of an oral formulation and a topical formulation to 18 male volunteers [TSD No. 7224]. Helsinn Healthcare, 1998. (Data on file).Google Scholar
  79. 79.
    Berardesca E. Evaluation of skin irritation and sensitization potential of different nimesulide topical formulations by repeated insult patch test in healthy volunteers [TSD No. 6103]. Helsinn Healthcare, 1998. (Data on file).Google Scholar
  80. 80.
    Saillant G. Multicenter, double-blind, parallel group study comparing the efficacy and tolerability of nimesulide gel 3% vs. placebo in the treatment of benign ankle sprains [TSD No. 7218]. Helsinn Healthcare, 1998. (Data on file).Google Scholar
  81. 81.
    Bourgeois P. Multicenter, double-blind, parallel group study comparing the efficacy and tolerability of nimesulide gel 3% vs. placebo in the treatment of tendinitis of the upper limb [TSD No. 7219]. Helsinn Healthcare, 1998. (Data on file).Google Scholar
  82. 82.
    Lücker PW. Study on the pharmacokinetics (single and multiple dose) of nimesulide in 10 elderly subjects [TSD No. 5619E]. Helsinn Healthcare, 1992. (Data on file).Google Scholar
  83. 83.
    Pontiroli AE. Report on the pharmacokinetics of nimesulide in elderly patients with normal and elevated creatinine plasma concentrations after single and repeated doses [TSD No. 5520E]. Helsinn Healthcare, 1991. (Data on file).Google Scholar
  84. 84.
    Fillastre JP Pharmacokinetics of nimesulide after single oral dose in patients with moderate renal insufficiency [TSD No. 4871E]. Helsinn Healthcare, 1991. (Data on file).Google Scholar
  85. 85.
    Fouarge M. Pharmacokinetic profile of nimesulide and its OH-metabolite in plasma and urine in 10 subjects with moderate renal failure during repeated oral administration [TSD No. 5611E]. Helsinn Healthcare, 1992. (Data on file).Google Scholar
  86. 86.
    Olive G. Pharmacokinetics of nimesulide after single oral administration to healthy subjects and those with hepatic insufficiency [TSD No. 5498E]. Helsinn Healthcare, 1993. (Data on file).Google Scholar
  87. 87.
    Perucca E. Drug interactions with nimesulide. Drugs 1993; 46 Suppl. 1: 79–82.PubMedCrossRefGoogle Scholar
  88. 88.
    Fouarge M. Pharmacokinetic interaction study between nimesulide and glibenclamide after single dose cross-over administration in 12 healthy subjects [TSD No. 5687E]. Helsinn Healthcare, 1993. (Data on file).Google Scholar
  89. 89.
    Ugazio G. Pharmacokinetic interaction study between nimesulide tablets and cimetidine tablets after single dose administration to 12 healthy volunteers [TSD No. 5691E]. Helsinn Healthcare, 1993. (Data on file).Google Scholar
  90. 90.
    Ugazio G. Pharmacokinetic interaction study between nimesulide tablets and Maalox suspension after single dose administration to 12 healthy volunteers [TSD No. 5692E]. Helsinn Healthcare, 1993. (Data on file).Google Scholar
  91. 91.
    Steinhauslin F, Munafo A, Buclin T, et al. Renal effects of nimesulide in furosemide-treated subjects. Drugs 1993; 46 Suppl. 1: 257–62.PubMedCrossRefGoogle Scholar
  92. 92.
    Auteri A, Bruni F, Pasqui AL, et al. Pharmacokinetics and pharmacodynamics of slow-release theophylline during treatment with nimesulide. Int J Clin Pharmacol Res 1991; 11: 211–8.PubMedGoogle Scholar
  93. 93.
    Lücker PW. Report of the study on the possible drug-drug interaction of warfarin and nimesulide in 12 healthy male volunteers [TSD No. 5686E]. Helsinn Healthcare, 1993. (Data on file).Google Scholar
  94. 94.
    Baggio E, Maraffi F, Montalto C, et al. A clinical assessment of the potential for pharmacological interaction between nimesulide and digoxin in patients with heart failure. Drugs 1993; 46 Suppl. 1: 91–4.PubMedCrossRefGoogle Scholar

Copyright information

© Adis International Limited 1998

Authors and Affiliations

  1. 1.Department of Pharmacokinetics and BiochemistryBoehringer Mannheim Italie, Research CentreMonzaItaly

Personalised recommendations