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Clinical Pharmacokinetics of Naproxen

  • Review Article
  • Drug Disposition
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Summary

Naproxen is a stereochemically pure nonsteroidal anti-inflammatory drug of the 2-arylpropionic acid class. The absorption of naproxen is rapid and complete when given orally. Naproxen binds extensively, in a concentration-dependent manner, to plasma albumin. The area under the plasma concentration-time curve (AUC) of naproxen is linearly proportional to the dose for oral doses up to a total dose of 500mg. At doses greater than 500mg there is an increase in the unbound fraction of drug, leading to an increased renal clearance of total naproxen while unbound renal clearance remains unchanged.

Substantial concentrations of the drug are attained in synovial fluid, which is a proposed site of action for nonsteroidal anti-inflammatory drugs. Relationships between the total and unbound plasma concentration, unbound synovial fluid concentration and therapeutic effect have been established.

Naproxen is eliminated following biotransformation to glucuroconjugated and sulphate metabolites which are excreted in urine, with only a small amount of the drug being eliminated unchanged. The excretion of the 6-O-desmethylnaproxen metabolite conjugate may be tied to renal function, as accumulation occurs in end-stage renal disease but does not appear to be influenced by age.

Hepatic disease and rheumatoid arthritis can also significantly alter the disposition kinetics of naproxen. Although naproxen is excreted into breast milk, the amount of drug transferred comprises only a small fraction of the maternal exposure.

Significant drug interactions have been demonstrated for probenecid, lithium and methotrexate.

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References

  1. Tomlinson RW, Ringold HG, Quereshi MC, et al. Relationship between inhibition of prostaglandin synthesis and drug efficacy: support for the current theory on mode of action of aspirin-like drugs. Biochem Biophys Res Commun 1972; 46: 552–9

    PubMed  CAS  Google Scholar 

  2. Brogden RN, Pinder RM, Sawyer PR, et al. Naproxen: a review of its pharmacological properties and therapeutic efficacy and use. Drugs 1975; 9: 326–63

    PubMed  CAS  Google Scholar 

  3. Brogden RN, Heel RC, Speight TM, et al. Naproxen up to date: a review of its pharmacological properties and therapeutic efficacy and use in rheumatic diseases and pain states. Drugs 1979; 18: 241–77

    PubMed  CAS  Google Scholar 

  4. Todd PA, Clissold SP. Naproxen: a reappraisal of its pharmacology, and therapeutic use in rheumatic diseases and pain states. Drugs 1990; 40(1): 91–137

    PubMed  CAS  Google Scholar 

  5. Pini LA, Bertolotti M, Trenti T, et al. Disposition of naproxen after oral administration during and between migraine attacks. Headache 1993; 33: 191–4

    PubMed  CAS  Google Scholar 

  6. Jamali F, Brocks DR. Clinical pharmacokinetics of ketoprofen and its enantiomers. Clin Pharmacokinet 1990; 19(3): 197–217

    PubMed  CAS  Google Scholar 

  7. Brocks DR, Jamali F. Clinical pharmacokinetics of ketorolac tromethamine. Clin Pharmacokinet 1992; 23(6): 415–27

    PubMed  CAS  Google Scholar 

  8. Evans AM. Enantioselective pharmacodynamics and pharmacokinetics of chiral non-steroidal anti-inflammatory drugs. Eur J Clin Pharmacol 1992; 42: 237–56

    PubMed  CAS  Google Scholar 

  9. Brocks DR, Jamali F. Etodolac clinical pharmacokinetics. Clin Pharmacokinet 1994; 26(4): 259–74

    PubMed  CAS  Google Scholar 

  10. Davies NM. Clinical pharmacokinetics of flurbiprofen and its enantiomers. Clin Pharmacokinet 1995; 28(2): 100–14

    PubMed  CAS  Google Scholar 

  11. Davies NM. Clinical pharmacokinetics of tiaprofenic acid and its enantiomers. Clin Pharmacokinet 1996; 31(5): 331–47

    PubMed  CAS  Google Scholar 

  12. Sevelius H, Runkel R, Pardo A, et al. Naproxen suppository: tissue response and comparative bioavailability. Eur J Clin Pharmacol 1973; 6: 22–5

    PubMed  CAS  Google Scholar 

  13. Ansell BM, Hanna DB, Stoppard M. Naproxen absorption in children. Curr Med Res Opin 1975; 3(1): 46–50

    PubMed  CAS  Google Scholar 

  14. Desager JP, Vanderbist M, Harvengt C. Naproxen plasma levels in volunteers after single-dose administration by oral and rectal routes. J Clin Pharmacol 1976; 16: 189–93

    PubMed  CAS  Google Scholar 

  15. Runkel R, Chaplin M, Sevelius H, et al. Pharmacokinetics of naproxen overdoses. Clin Pharmacol Ther 1976; 20(3): 269–77

    PubMed  CAS  Google Scholar 

  16. Runkel R, Mroszczak E, Chaplin M, et al. Naproxen-probenecid interaction. Clin Pharmacol Ther 1978; 24(6): 706–13

    PubMed  CAS  Google Scholar 

  17. Calvo MV, Dominguez-Gil A, Miralies JM, et al. Pharmacokinetics of naproxen in healthy volunteers and in patients with diabetic microangiopathy. Int J Clin Pharmacol Biopharm 1979; 17(12): 486–91

    PubMed  CAS  Google Scholar 

  18. Antilla M, Haataja M, Kasanen A. Pharmacokinetics of naproxen in subjects with normal and impaired renal function. Eur J Clin Pharmacol 1980; 18: 263–8

    Google Scholar 

  19. Calvo MV, Dominguez-Gil A, Macias JG, et al. Naproxen disposition in hepatic and biliary disorders. Int J Clin Pharmacol Ther Toxicol 1980; 18(6): 242–6

    PubMed  CAS  Google Scholar 

  20. Calvo MV, Dominguez-Gil A, Muriel C. Pharmacokinetics of naproxen in patients with hypoproteinemia. Int J Clin Pharmacol Ther Toxicol 1981; 19(7): 326–30

    PubMed  CAS  Google Scholar 

  21. Weber SS, Bankhurst AD, Mroszczak E, et al. Effect of Mylanta® on naproxen bioavailability. Ther Drug Monit 1981; 3: 75–83

    PubMed  CAS  Google Scholar 

  22. Kauffmann RE, Bolliger RO, Wan SH, et al. Pharmacokinetics and metabolism of naproxen in children. Dev Pharmacol Ther 1982; 5(3–4): 143–50

    PubMed  CAS  Google Scholar 

  23. Aarbakke J, Gadeholt G, Høylandskjær A. Pharmacokinetics of naproxen after oral administration of two tablet formulations in healthy volunteers. Int J Clin Pharmacol Ther Toxicol 1983; 21(6): 281–3

    PubMed  CAS  Google Scholar 

  24. Calvo MV, Dominguez-Gil A. Interaction of naproxen with cholestyramine. Biopharm Drug Dispos 1984; 5: 33–42

    PubMed  CAS  Google Scholar 

  25. Gamst ON, Haga AK, Holler T, et al. Absorption of naproxen from enteric coated tablets. Nor Pharm Acta 1984; 46: 1–15

    CAS  Google Scholar 

  26. Gamst ON, Vesje AK, Aarbakke J. Bioavailability of naproxen sodium suppositories. Int J Clin Pharmacol Ther Toxicol 1984; 22(2): 99–103

    PubMed  CAS  Google Scholar 

  27. Upton RA, Williams RL, Kelly J, et al. Naproxen pharmacokinetics in the elderly. Br J Clin Pharmacol 1984; 18: 207–14

    PubMed  CAS  Google Scholar 

  28. Williams RL, Upton RA, Cello JP, et al. Naproxen disposition in patients with alcoholic cirrhosis. Eur J Clin Pharmacol 1984; 27: 291–6

    PubMed  CAS  Google Scholar 

  29. Franssen MJAM, Tan Y, van De Putte CAM, et al. Pharmacokinetics of naproxen at two dosage regimens in healthy volunteers. Int J Clin Pharmacol Ther Toxicol 1986; 24(3): 139–42

    PubMed  CAS  Google Scholar 

  30. McVerry RM, Lethbridge J, Martin N, et al. Pharmacokinetics of naproxen in elderly patients. Eur J Clin Pharmacol 1986; 31: 463–8

    PubMed  CAS  Google Scholar 

  31. Van Den Ouweland FA, Gribnau FWJ, Tan Y, et al. Hypoalbuminemia and naproxen pharmacokinetics in a patient with rheumatoid arthritis. Clin Pharmacokinet 1986; 11: 511–5

    PubMed  Google Scholar 

  32. Caillé G, Du Souich P, Gervais P, et al. Effects of concurrent sucralfate administration on pharmacokinetics of naproxen. Am J Med 1987; 83 Suppl. 3B: 67–71

    PubMed  Google Scholar 

  33. Caillé G, Du Souich P, Gervais P, et al. Single dose pharmacokinetics of ketoprofen, indomethacin, and naproxen taken alone or with sucralfate. Biopharm Drug Dispos 1987; 8: 173–83

    PubMed  Google Scholar 

  34. Constantine G, Hale K, Brennan C, et al. Vaginal absorption of naproxen. J Clin Pharm Ther 1987; 12: 193–6

    PubMed  CAS  Google Scholar 

  35. Ling TL, Yee JP, Cohen A, et al. A multiple-dose pharmacokinetic comparison of naproxen as a once-daily controlled-release and a twice-daily conventional tablet. J Clin Pharmacol 1987; 27: 325–9

    PubMed  CAS  Google Scholar 

  36. Van Den Ouweland FA, Franssen MJAM, Van De Putte LBA, et al. Naproxen pharmacokinetics in patients with rheumatoid arthritis during active polyarticular inflammation. Br J Clin Pharmacol 1987; 23: 189–93

    PubMed  Google Scholar 

  37. Berté F, Feletti F, De Bernardi di Valserra M, et al. Lack of influence of sulglycotide on naproxen bioavailability in healthy volunteers. Int J Clin Pharmacol Ther Toxicol 1988; 26(3): 125–8

    PubMed  Google Scholar 

  38. Cohen A, Gonzalez MA, Mroszczak EJ, et al. Evaluation of the pharmacokinetics of naproxen from a 500-mg controlled-release tablet. Curr Ther Res 1988; 43(6): 1109–17

    CAS  Google Scholar 

  39. Blagbrough IS, Daykin MM, Doherety M, et al. Synovial fluid and plasma levels of naproxen in osteoarthritis [abstract]. J Pharm Pharmacol 1988; 40 Suppl. C: 153

    Google Scholar 

  40. Cohen A, Basch C. Steady state pharmacokinetics of naproxen in young and elderly healthy volunteers. Semin Arthritis Rheum 1988; 17(3) Suppl. 2: 7–11

    PubMed  CAS  Google Scholar 

  41. Gøtzsche PC, Andreasen F, Egsmose CH, et al. Steady state pharmacokinetics of naproxen in elderly rheumatics compared with young volunteers. Scand J Rheumatol 1988; 17: 11–6

    PubMed  Google Scholar 

  42. Guelen PJM, Janssen TJ, Brueren MM, et al. The pharmacokinetic profile of naproxen suppository in man. Int J Clin Pharmacol Ther Toxicol 1988; 26(4): 190–3

    PubMed  CAS  Google Scholar 

  43. Mroszczak E, Yee JP, Bynum L. Absorption of naproxen controlled-release tablets in fasting and postprandial volunteers. J Clin Pharmacol 1988; 28: 1128–31

    PubMed  CAS  Google Scholar 

  44. Ryley NJ, Lingman G. A pharmacokinetic comparison of controlled-release and standard naproxen tablets. Curr Med Res Opin 1988; 11(1): 10–5

    PubMed  CAS  Google Scholar 

  45. Van Den Ouweland FA, Jansen PAF, Tan Y, et al. Pharmacokinetics of high-dose naproxen in elderly patients. Int J Clin Pharmcol Ther Toxicol 1988; 26(3): 143–7

    Google Scholar 

  46. Kelly JG, Kinney CD, Mulligan S, et al. Pharmacokinetic properties and clinical efficacy of once-daily sustained-release naproxen. Eur J Clin Pharmacol 1989; 36: 383–8

    PubMed  CAS  Google Scholar 

  47. Dahl T, Ling T, Bormeth A. Effects of various granulating systems on the bioavailability of naproxen sodium from polymeric matrix tablets. J Pharm Sci 1990; 79(5): 389–92

    PubMed  CAS  Google Scholar 

  48. Lafontaine D, Mailhot C, Vermeulen M, et al. Influence of chewable sucralfate or a standard meal on the bioavailability of naproxen. Clin Pharm 1990; 9: 773–7

    PubMed  CAS  Google Scholar 

  49. Palazzini E, Galli G, Babbini M. Multiple-dose pharmacokinetics of naproxen from a controlled-release tablet in healthy volunteers. Int J Clin Pharmacol Res 1990; 10(5): 277–84

    PubMed  CAS  Google Scholar 

  50. Hardy JG, Lamont GL, Evans DF, et al. Evaluation of an enteric-coated naproxen pellet formulation. Aliment Pharmacol Ther 1991; 5: 69–75

    PubMed  CAS  Google Scholar 

  51. Strocchi E, Ambrosioni E, Palazzini E, et al. Pharmacokinetics of a controlled release preparation of naproxen. Int J Clin Pharmacol Ther Toxicol 1991; 29(7): 253–6

    PubMed  CAS  Google Scholar 

  52. Walson PD, Kelley MT, Mortensen ME. Pharmacokinetics of naproxen tablets and naproxen suspension in febrile adults and children. Clin Ther 1991; 13 Suppl. A: 26–34

    Google Scholar 

  53. Palazzini E, Cristofori M, Babbini M. Bioavailability of a new controlled-release oral naproxen formulation given with and without food. Int J Clin Pharmacol Res 1992; 22(4): 179–84

    Google Scholar 

  54. Rao BR, Rambhau D, Rao VVS. Pharmacokinetics of single-dose administration of naproxen at 10:00 and 22:00 hours. Chronobiol Int 1992; 10(2): 137–42

    Google Scholar 

  55. Wilding IR, Hardy JG, Sparrow RA, et al. In vivo evaluation of enteric-coated naproxen tablets using gamma scintigraphy. Pharm Res 1992; 9(11): 1436–41

    PubMed  CAS  Google Scholar 

  56. Sastry MSP, Diwan PV. Comparative pharmacokinetic evaluation of compressed naproxen suppositories in humans. Arzneimittel Forschung 1993; 43(11): 1209–10

    PubMed  CAS  Google Scholar 

  57. Vree TB, Van Den Biggelaar-Martea M, Corrien PWGM, et al. Pharmacokinetics of naproxen, its metabolite O-desmethylnaproxen, and their acyl glucuronides in humans. Biopharm Drug Dispos 1993; 14: 491–502

    PubMed  CAS  Google Scholar 

  58. Charles BG, Mogg GAG. Comparative in vitro and in vivo bioavailability of naproxen from tablet and caplet formulations. Biopharm Drug Dispos 1994; 15: 121–8

    PubMed  CAS  Google Scholar 

  59. Jung D, Schwartz KE. Steady-state pharmacokinetics of enteric-coated naproxen tablets compared with standard naproxen tablets. Clin Ther 1994; 16(6): 923–9

    PubMed  CAS  Google Scholar 

  60. Wells TG, Mortensen ME, Dietrich A, et al. Comparison of the pharmacokinetics of naproxen tablets and suspension in children. J Clin Pharmacol 1994; 34: 30–3

    PubMed  CAS  Google Scholar 

  61. Awni WM, Braeckman RA, Cavanagh JH, et al. The pharmacokinetic and pharmacodynamic interactions between 5-lipoxygenase inhibitor zileuton and the cyclo-oxygenase inhibitor naproxen in human volunteers. Clin Pharmacokinet 1996; 29 Suppl. 2: 112–24

    Google Scholar 

  62. Niazi S, Alam M, Ahmad SI. Dose dependent pharmacokinetics of naproxen in man. Biopharm Drug Dispos 1996; 17: 355–61

    PubMed  CAS  Google Scholar 

  63. Runkel RA, Kraft KS, Boost G. Naproxen oral absorption characteristics. Chem Pharm Bull 1972; 20(7): 1457–66

    PubMed  CAS  Google Scholar 

  64. Runkel R, Chaplin M, Boost G, et al. Absorption, distribution, metabolism, and excretion of naproxen in various laboratory animals and human subjects. J Pharm Sci 1972; 61(5): 703–8

    PubMed  CAS  Google Scholar 

  65. Sevelius H, Runkel R, Segre E, et al. Bioavailability of naproxen sodium and its relationship to clinical analgesic effects. Br J Clin Pharmacol 1980; 10: 259–63

    PubMed  CAS  Google Scholar 

  66. Gamst ON. Oral naproxen formulations. Scand J Gastroenterol 1989; 24 Suppl. 163: 44–7

    Google Scholar 

  67. Palazzini E, Galli G, Babbini M. Pharmacokinetic evaluation of conventional and controlled-release product of naproxen. Drugs Exp Clin Res 1990; 24(5): 243–7

    Google Scholar 

  68. Berry H, Swinson D, Jones J, et al. Indomethacin and naproxen suppositories in the treatment of rheumatoid arthritis. Ann Rheum Dis 1978; 37: 370–2

    PubMed  CAS  Google Scholar 

  69. Gøtzsche PC, Marinelli K, Gylding-Sabroe JP, et al. Bioavailability of naproxen tablets and suppositories in steady state. Scand J Rheumatol 1983; 12 Suppl. 50: 2–9

    Google Scholar 

  70. Van Den Ouweland FA, Eenhoorn PC, Tan Y, et al. Transcutaneous absorption of naproxen gel. Br J Clin Pharmacol 1989; 36: 209–11

    Google Scholar 

  71. Segre EJ, Sevelius H, Varady J. Effects of antacids on naproxen absorption. N Eng J Med 1974; 291: 582–3

    CAS  Google Scholar 

  72. Vree TB, Van Den Biggelaar-Martea M, Verwey-Van Wissen CPWGM, et al. The effects of cimetidine, ranitidine and famotidine on the single-dose pharmacokinetics of naproxen and its metabolites in humans. Int J Clin Pharmacol Ther Toxicol 1993; 31(12): 597–601

    PubMed  CAS  Google Scholar 

  73. Vree TB, Van Den Biggelaar-Martea M, Verwey-Van Wissen CPWGM, et al. The pharmacokinetics of naproxen, its metabolite O-desmethylnaproxen, and their acyl glucuronides in humans. Effect of cimetidine. Br J Clin Pharmacol 1993; 35: 467–72

    PubMed  CAS  Google Scholar 

  74. Day RO, Francis H, Vial J, et al. Naproxen concentrations in plasma and synovial fluid and effects on prostanoid concentrations. J Rheumatol 1995; 22: 2295–303

    PubMed  CAS  Google Scholar 

  75. Ellis DJ, Martin B. The plasma protein binding properties of a new non-steroidal anti-inflammatory agent [abstract]. Fed Proc 1971; 30: 1200

    Google Scholar 

  76. Piafsky KM, Borgå O. Plasma protein binding of basic drugs. II. Importance of α1-acid glycoprotein for interindividual variation. Clin Pharmacol Ther 1977; 22: 545–9

    PubMed  CAS  Google Scholar 

  77. Mortensen A, Bjørn Jensen E, Bernth-Petersen P, et al. The determination of naproxen by spectrofluorometry and its binding to serum proteins. Acta Pharmacol Toxicol 1979; 44: 277–83

    CAS  Google Scholar 

  78. Calvo MV, Dominguez-Gil A. Binding of naproxen to human albumin, interaction with palmitic acid. Int J Pharm 1983; 16: 215–23

    CAS  Google Scholar 

  79. Pase U, Tafuro A. Farmacocinetica del naprossene sodico nel siero e nella saliva di individui sani. G Stomatol Ortognatodonzia 1984; 3(3): 364–5

    PubMed  CAS  Google Scholar 

  80. Runkel R, Forchilelli E, Sevelius H, et al. Nonlinear plasma level response to high doses of naproxen. Clin Pharmacol Ther 1973; 15(3): 261–6

    Google Scholar 

  81. Held H. Elimination shalbwertszeiten und serumproteinbindung des antirheumatikums naproxen bei niereninsuffizienz. Z Rheumatol 1979; 38: 111–9

    PubMed  CAS  Google Scholar 

  82. Held H. Serumproteinbindung und eliminationshalbwertszeiten von naproxen bei patienten mit hepatozellularem bzw. obstruktivem ikterus. Arzneimittel Forschung 1980; 30(1): 843–6

    PubMed  CAS  Google Scholar 

  83. Jain A, McMahon FG, Slattery JT, et al. Effect of naproxen on the steady-state serum concentration and anticoagulant activity of warfarin. Clin Pharmacother 1979; 22: 61–6

    Google Scholar 

  84. Jalava S, Saarimaa H, Anttilla M, et.al. Naproxen concentrations in serum synovial fluid, and synovium. Scand J Rheumatol 1977; 6: 155–7

    PubMed  CAS  Google Scholar 

  85. Katona G, Burgos R, Ortega E. Pharmacokinetics of a single dose of naproxen in plasma and synovial fluid. In: Naproxen. Proceedings of Symposium held in conjunction with the IX European Congress of Rheumatology. 1980 Sep 1–6; Wiesenbaden, Germany. Excerpta Medical Foundation, 1980; 41–5

    Google Scholar 

  86. Dougados M, Coste PH, Stalla-Bourdillon AS, et al. Influence de la nature de lépanchement articulaire sur la diffusion des anti-inflammatoires non stéroïdiens à travers la membrane synoviale: a propos du naproxène sodique 550 mg au cours de la polyarthrite rhumatoïde et la gonarthrose. Rev Intern Rheumatologie‘R’ 1986; 16: 105–9

    Google Scholar 

  87. Bruno R, Iliadis A, Jullien I, et al. Naproxen kinetics in synovial fluid of patients with osteoarthritis. Br J Clin Pharmacol 1988; 26: 41–4

    PubMed  CAS  Google Scholar 

  88. Renier JC, Masson CH, Baudel F, et al. Pharmacocinétique plasmatique, synoviale et intra-articulaire du naproxène après administration orale dun gramme chez des sujets atteints de polyarthritique rheumatoïde. Rev Rhum 1988; 55(6): 435–9

    PubMed  CAS  Google Scholar 

  89. Dougados M, Coste PH, Amor B. Dosage du naproxène sodique dans le sang et dans le liquide synovial après administration de deux comprimés à 550 mg en une prise au cours de la polyarthrite rhumatoïde. J Int Med Rhumatol Mondial 1985; 10 Suppl. 56: 21–33

    Google Scholar 

  90. Bannwarth B, Schaeverbeke T, Demotes-Mainard F, et al. Naproxen distribution in joint tissues [abstract]. Clin Pharmacol Ther 1995; 57(2): 158 PI-94

    Google Scholar 

  91. Bertin P, Lapique F, Payan E, et al. Sodium naproxen: concentration and effect on inflammatory response mediators in human rheumatoid synovial fluid. Eur J Clin Pharmacol 1994; 46: 3–7

    PubMed  CAS  Google Scholar 

  92. Newlands AJ, Smith DA, Jones BC, et al. Metabolism of non-steroidal anti-inflammatory drugs by cytochrome P450 2C [abstract]. Br J Clin Pharmacol 1992; 34: 152P

    Google Scholar 

  93. Miners JO, Coulter S, Tukey RH, et al. Cytochrome P450,1A2, and 2C9 are responsible for the human hepatic O-demethylation of R-and S-naproxen. Biochem Pharmacol 1996; 51: 1003–8

    PubMed  CAS  Google Scholar 

  94. Sugarawa Y, Fujihara M, Miura K, et al. Studies on the fate of naproxen II. Metabolic fate in various animals and man. Chem Pharm Bull 1978; 26: 3312–21

    Google Scholar 

  95. Kuramoto M, Ishimura Y, Okubo T, et al. Toxicity of naproxen, acute and subacute toxicity in mice and rats. Shikoku Acta Med 1973; 29: 439–53

    CAS  Google Scholar 

  96. Winter CA, Risley EA, Nuss GW. Carrageenan induced edema in the hind paw of the rat as an assay for anti-inflammatory drugs. Proc Soc Exp Biol Med 1962; 111: 544–9

    PubMed  CAS  Google Scholar 

  97. Kiang C-H, Lee C, Kushinsky S. Isolation and identification of 6-desmethylnaproxen sulfate as a new metabolite of naproxen in human plasma. Drug Metab Dispos 1989; 17(1): 43–8

    PubMed  CAS  Google Scholar 

  98. Jamali F, Stevens DRS. Naproxen excretion in milk and its uptake by the infant. Drug Intell Clin Pharm 1983; 17: 910–1

    PubMed  CAS  Google Scholar 

  99. Day RO, Furst DE, Dromgoole SH, et al. Relationship of serum naproxen concentration to efficacy in rheumatoid arthritis. Clin Pharmacol Ther 1982; 31: 733–40

    PubMed  CAS  Google Scholar 

  100. Dunagan FM, McGill PE, Kelman AW, et al. Naproxen dose and concentration: response relationship in rheumatoid arthritis. Br J Rheumatol 1988; 27: 48–53

    PubMed  CAS  Google Scholar 

  101. Day RO, Graham GG, Williams KM, et al. Variability in response to NSAIDs: fact or fiction? Drugs 1988; 36: 643–51

    PubMed  CAS  Google Scholar 

  102. Gérard MJ. Individual variation in the response to nonsteroidal anti-inflammatory drugs. Rev Rhum Mal Osteoartic 1988; 55: 735–9

    PubMed  Google Scholar 

  103. Hoyeraal HM, Fagertun H, Ingemann-Hansen T, et al. Characterization of responders and nonresponders to tiaprofenic acid and naproxen in the treatment of patients with osteoarthritis. J Rheumatol 1993; 20(10): 1747–52

    PubMed  CAS  Google Scholar 

  104. Hoyo-Vadillo C, Perez-Urizar JT, Garcia I, et al. Relationship between plasma levels of naproxen and analgesic efficacy in rats: synergism with caffeine. Proc West Pharmacol Soc 1994; 37: 91–2

    PubMed  CAS  Google Scholar 

  105. Johnsen V, Bjerkhoel F, Bjorneboe O, et al. Duration of morning stiffness in rheumatic patients after medication with enteric-coated and plain naproxen tablets. Scand J Rheumatol 1986; 15: 37–40

    PubMed  CAS  Google Scholar 

  106. Rugstad HE, Hundal O, Holme I, et al. Piroxicam and naproxen concentrations in patients with osteoarthritis: relation to age, sex, efficacy and adverse events. Clin Rheumatol 1986; 5(3): 389–98

    PubMed  CAS  Google Scholar 

  107. Sacerdote P, Carrabba M, Galante A, et al. Plasma and synovial fluid interleukin-1, interleukin-6 and substance P concentrations in rheumatoid arthritis patients: effect of the nonsteroidal anti inflammatory drugs indomethacin, naproxen and naproxen. Inflamm Res 1995; 44(11): 486–90

    PubMed  CAS  Google Scholar 

  108. Van Den Ouweland FA, Gribnau FWJ, Van Ginneken CAM, et al. Naproxen kinetics and disease activity in rheumatoid arthritis: a within-patient study. Clin Pharmacol Ther 1988; 43: 79–85

    PubMed  Google Scholar 

  109. Weber SS, Troutman WG, Trujeque L. Effect of hemodialysis on plasma naproxen concentration. Am J Hosp Pharm 1979; 36: 1567–9

    PubMed  CAS  Google Scholar 

  110. Watson WA, Freer JP, Katz RS, et al. Kidney function during naproxen therapy in patients at risk for renal insufficiency. Semin Arthritis Rheum 1988; 17(3): 12–6

    PubMed  CAS  Google Scholar 

  111. Shankel SW, Johnson DC, Clark PS, et al. Acute renal failure and glomerulopathy caused by nonsteroidal anti-inflammatory drugs. Arch Intern Med 1992; 152(5): 986–90

    PubMed  CAS  Google Scholar 

  112. Wibell L. The metabolism of naproxen in renal insufficiency. Scand J Rheumatol 1977; 6: 71–2

    Google Scholar 

  113. Mäkelä A-L. Naproxen in the treatment of juvenile rheumatoid arthritis: metabolism, safety, and efficacy. Scand J Rheumatol 1977; 6: 193–205

    PubMed  Google Scholar 

  114. Mäkelä A-L. The metabolism of naproxen in children. Scand J Rheumatol 1977; 6: 77–8

    Google Scholar 

  115. Brouwers JR, de Smet PA. Pharmacokinetic-pharmacodynamic drug interactions with nonsteroidal anti-Inflammatory drugs. Clin Pharmacokinet 1994; 27: 462–85

    PubMed  CAS  Google Scholar 

  116. Upton RA, Buskin JN, Williams RL, et al. Negligible excretion of unchanged ketoprofen, naproxen, and probenecid in urine. J Pharm Sci 1980; 69(11): 1254–7

    PubMed  CAS  Google Scholar 

  117. Henry D, Dobson A, Turner C. Variability in the risk of major gastrointestinal complications from nonaspirin nonsteroidal anti-inflammatory drugs. Gastroenterology 1993; 105: 1078–88

    PubMed  CAS  Google Scholar 

  118. Lichtenstein DR, Syngal S, Wolfe MM. Nonsteroidal anti-inflammatory drugs and the gastrointestinal tract: the doubleedged sword. Arthritis Rheum 1995; 38: 5–18

    PubMed  CAS  Google Scholar 

  119. Segre EJ, Chaplin M, Forchielli E, et al. Naproxen-aspirin interactions in man. Clin Pharmacol Ther 1973; 15(2): 374–9

    Google Scholar 

  120. Dresse A, Gerard MA, Quinaux N, et al. Effect of diflunisal on the human plasma levels and on the urinary excretion of naproxen. Arch Int Pharmacodyn Ther 1978; 236: 276–84

    PubMed  CAS  Google Scholar 

  121. Furst DE, Blocka K, Cassell S, et al. A controlled study of concurrent therapy with a nonacetylated salicylate and naproxen in rheumatoid arthritis. Arthritis Rheum 1987; 30(2): 146–54

    PubMed  CAS  Google Scholar 

  122. Furst DE, Sarkissian E, Blocka K, et al. Serum concentrations of salicylate and naproxen during concurrent therapy in patients with rheumatoid arthritis. Arthritis Rheum 1987; 30(10): 1157–61

    PubMed  CAS  Google Scholar 

  123. Slattery JT, Levy G, Jain A, et al. Effect of naproxen on the kinetics of elimination and anticoagulant activity of a single dose of warfarin. Clin Pharmacol Ther 1979; 25(1): 51–60

    PubMed  CAS  Google Scholar 

  124. Wallace CA, Smith AL, Sherry DD. Pilot investigation of naproxen/methotrexate interaction in patients with juvenile rheumatoid arthritis. J Rheumatol 1993; 20(10): 1764–8

    PubMed  CAS  Google Scholar 

  125. Fiesco AL, Herrera JE, Rodriguez JM, et al. Bioequivalence of new combination of naproxen sodium plus psudoepehedrine capsules in a mexican population. Proc West Pharmacol Soc 1994; 37: 161–2

    Google Scholar 

  126. Sachse VG, Becker WR. Untersuchungen zur interaktion zwischen naproxen und tolbutamid um hinblick auf die stoffwechsellage des diabetikers. Arzneimittel Forschung 1979; 29(1): 835–6

    PubMed  CAS  Google Scholar 

  127. Grimaldi R, Lecchini S, Crema F, et al. In vivo plasma protein binding interaction between valproic acid and naproxen. Eur J Drug Metab Pharmacokinet 1984; 9(4): 359–63

    PubMed  CAS  Google Scholar 

  128. Dasgupta A, Volk A. Displacement of valproic acid and carbamazepine from protein binding in normal and uremic sera by tolmetin, ibuprofen, and naproxen: presence of inhibiotor in uremic serum that blocks valproic acid-naproxen interactions. Ther Drug Monit 1996; 18(3): 284–7

    PubMed  CAS  Google Scholar 

  129. Yacobi A, Levy G. Effect of naproxen on protein binding of warfarin in human serum. Res Commun Chem Pathol Pharmacol 1976; 15(2): 369–72

    PubMed  CAS  Google Scholar 

  130. Sahai J, Gallicano K, Garber G, et al. Evaluation of the in vivo effect of naproxen on zidovudine pharmacokinetics in patients infected with human immunodeficiency virus. Clin Pharmacol Ther 1992; 52: 464–70

    PubMed  CAS  Google Scholar 

  131. Barry M, Howe J, Back D, et al. The effects of indomethacin and naproxen on zidovudine pharmacokinetics. Br J Clin Pharmacol 1993; 36: 82–5

    PubMed  CAS  Google Scholar 

  132. Sim SM, Black DJ, Breckenridge AM. The effect of various drugs on the glucoronidation of zidovudine (azidothymidine; AZT) by human liver microsomes. Br J Clin Pharmacol 1991; 32: 17–21

    PubMed  CAS  Google Scholar 

  133. Singh RR, Malaviya AN, Pandey JN, et al. Fatal interaction between methotrexate and naproxen [letter]. Lancet 1986; I: 1390

    Google Scholar 

  134. Slørdal L, Sager G, Jaeger R, et al. Interactions with the protein binding of 7-hydroxy-methotrexate in human serum in vitro. Biochem Pharmacol 1988; 37(4): 607–11

    PubMed  Google Scholar 

  135. Tracy TS, Krohn K, Bradley JD, et al. The effects of a salicylate, ibuprofen, and naproxen on the disposition of methotrexate in patients with rheumatoid arthritis. Eur J Clin Pharmacol 1992; 42: 121–5

    PubMed  CAS  Google Scholar 

  136. Ahern M, Booth J, Loxton A, et al. Methotrexate kinetics in rheumatoid arthritis: is there an interaction with nonsteroidal antiinflammatory drugs? J Rheumatol 1988; 15(9): 1356–60

    PubMed  CAS  Google Scholar 

  137. Stewart CF, Fleming RA, Arkin CR, et al. Coadministration of naproxen and low-dose methotrexate in patients with rheumatoid arthritis. Clin Pharmacol Ther 1990; 47: 540–6

    PubMed  CAS  Google Scholar 

  138. Bannwarth B, Labat L, Moride Y, et al. Methotrexate in rheumatoid arthritis. An update. Drugs 1994; 47(1): 25–50

    PubMed  CAS  Google Scholar 

  139. Ragheb M, Powell AL. Lithium interaction with sulindac and naproxen. J Clin Psychopharmacol 1986; 6(3): 150–4

    PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Faculty of Medicine, Department of Pharmacology and Therapeutics, University of Calgary, Calgary, Alberta, T2N 4N1, Canada

    Neal M. Davies

  2. Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada

    Keith E. Anderson

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  1. Neal M. Davies
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  2. Keith E. Anderson
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Correspondence to Neal M. Davies.

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Davies, N.M., Anderson, K.E. Clinical Pharmacokinetics of Naproxen. Clin-Pharmacokinet 32, 268–293 (1997). https://doi.org/10.2165/00003088-199732040-00002

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