Advertisement

Clinical Pharmacokinetics

, Volume 34, Issue 2, pp 101–154 | Cite as

Clinical Pharmacokinetics of Ibuprofen

The First 30 Years
  • Neal M. DaviesEmail author
Review Article Drug Disposition

Abstract

Ibuprofen is a chiral nonsteroidal anti-inflammatory drug (NSAID) of the 2 arylpropionic acid (2-APA) class. A common structural feature of 2-APA NSAIDs is a sp 3-hybridised tetrahedral chiral carbon atom within the propionic acid side chain moiety with the S-(+)-enantiomer possessing most of the beneficial anti-inflammatory activity. Ibuprofen demonstrates marked stereoselectivity in its pharmacokinetics. Substantial unidirectional inversion of the R-(−) to the S-(+) enantiomer occurs and thus, data generated using nonstereospecific assays may not be extrapolated to explain the disposition of the individual enantiomers.

The absorption of ibuprofen is rapid and complete when given orally. The area under the plasma concentration-time curve (AUC) of ibuprofen is dose-dependent. Ibuprofen binds extensively, in a concentration-dependent manner, to plasma albumin. At doses greater than 600mg there is an increase in the unbound fraction of the drug, leading to an increased clearance of ibuprofen and a reduced AUC of the total drug. Substantial concentrations of ibuprofen are attained in synovial fluid, which is a proposed site of action for nonsteroidal anti-inflammatory drugs.

Ibuprofen is eliminated following biotransformation to glucuronide conjugate metabolites that are excreted in urine, with little of the drug being eliminated unchanged. The excretion of conjugates may be tied to renal function and the accumulation of conjugates occurs in end-stage renal disease. Hepatic disease and cystic fibrosis can alter the disposition kinetics of ibuprofen. Ibuprofen is not excreted in substantial concentrations into breast milk.

Significant drug interactions have been demonstrated for aspirin (acetylsalicylic acid), cholestyramine and methotrexate. A relationship between ibuprofen plasma concentrations and analgesic and antipyretic effects has been elucidated.

Keywords

Adis International Limited Ibuprofen Synovial Fluid Sucralfate Racemate 
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.
    Adams SS, Cliffe EE, Lessel B, et al. Some biological properties of 2-(4-isobutylphenyl)propionic acid [short report]. J Pharm Sci. 1967; 56: 1686.PubMedCrossRefGoogle Scholar
  2. 2.
    Adams SS, Bresloff P, Mason CG. Pharmacological differences between the optical isomers of ibuprofen: evidence for metabolic inversion of the (−)-isomer. J Pharm Pharmacol. 1976; 28: 256–7.PubMedCrossRefGoogle Scholar
  3. 3.
    Geisslinger G, Stock KP, Bach GL, et al. Pharmacological differences between R(−)- and S(+)-ibuprofen. Agents Actions. 1989; 27: 455–7.PubMedCrossRefGoogle Scholar
  4. 4.
    Evans AM. Enantioselective pharmacodynamics and pharmacokinetics of chiral non-steroidal anti-inflammatory drugs. Eur J Clin Pharmacol. 1992; 42: 237–56.PubMedCrossRefGoogle Scholar
  5. 5.
    Villaneuva M, Heckenberger R, Strobach H, et al. Equipotent inhibition by R(−)-, S(+)- and racemic ibuprofen of human polymorphonuclear cell function in vitro. Br J Clin Pharmacol. 1993; 35: 235–42.CrossRefGoogle Scholar
  6. 6.
    Evans AM, Nation RL, Sansom LN, et al. Effect of racemic ibuprofen dose on the magnitude and duration of platelet cyclo-oxygenase inhibition: relationship between inhibition of thromboxane synthesis and the plasma unbound concentration of S(+)-ibuprofen. Br J Clin Pharmacol. 1991; 31: 131–8.PubMedCrossRefGoogle Scholar
  7. 7.
    Busson M. Update on ibuprofen: review article. J Int Med Res. 1986; 14: 53–62.PubMedGoogle Scholar
  8. 8.
    Davies EF, Avery GS. Ibuprofen: a review of its pharmacological properties and therapeutic efficacy in rheumatic disorders. Drugs. 1971; 2: 416–46.PubMedCrossRefGoogle Scholar
  9. 9.
    Verbeeck RK. Pathophysiologic factors affecting the pharmacokinetics of nonsteroidal antiinflammatory drugs. J Rheumatol 1988; 17 Suppl.: 44–57.Google Scholar
  10. 10.
    Davies NM. Clinical pharmacokinetics of flurbiprofen and its enantiomers. Clin Pharmacokinet. 1995; 28: 100–14.PubMedCrossRefGoogle Scholar
  11. 11.
    Davies NM. Clinical pharmacokinetics of tiaprofenic acid and its enantiomers. Clin Pharmacokinet. 1996; 31: 331–47.PubMedCrossRefGoogle Scholar
  12. 12.
    Brocks DR, Jamali F. Etodolac clinical pharmacokinetics. Clin Pharmacokinet. 1994; 26: 259–74.PubMedCrossRefGoogle Scholar
  13. 13.
    Brocks DR, Jamali F. Clinical Pharmacokinetics of ketorolac tromethamine. Clin Pharmacokinet. 1992; 23: 415–27.PubMedCrossRefGoogle Scholar
  14. 14.
    Jamali F, Brocks DR. Clinical pharmacokinetics of ketoprofen and its enantiomers. Clin Pharmacokinet. 1990; 19: 197–217.PubMedCrossRefGoogle Scholar
  15. 15.
    Davies NM, Anderson KE. Clinical pharmacokinetics of naproxen. Clin Pharmacokinet. 1997; 32: 268–93.PubMedCrossRefGoogle Scholar
  16. 16.
    Kaiser DG, Vangiessen GJ. GLC determination of ibuprofen [(±)-2-(p-isobutylphenyl)propionic acid in plasma. J Pharm Sci. 1974; 63: 219–21.PubMedCrossRefGoogle Scholar
  17. 17.
    Fujise H. A simple and sensitive colorimetric determination of ibuprofen from plasma and urine in dogs after dosing. Jpn J Vet Sci. 1977; 39: 671–3.CrossRefGoogle Scholar
  18. 18.
    Hoffman DJ. Rapid GLC determination of ibuprofen in serum. J Pharm Sci. 1977; 66: 749–50.PubMedCrossRefGoogle Scholar
  19. 19.
    Midha KK, Cooper JK, Hubbard JW, et al. A rapid and simple GLC procedure for determinations of plasma concentrations of ibuprofen. Can J Pharm Sci. 1977; 12: 29–31.Google Scholar
  20. 20.
    Hackett LP, Dusci LJ. Gas-liquid Chromatographic determination of ibuprofen in human plasma. Clin Chim Acta. 1978; 87: 301–3.PubMedCrossRefGoogle Scholar
  21. 21.
    Kaiser DG, Martin RS. Electron-capture GLC determination of ibuprofen in serum. J Pharm Sci. 1978; 67: 627–30.PubMedCrossRefGoogle Scholar
  22. 22.
    Singh NN, Pasutto FM, Coutts RT, et al. Gas Chromatographic separation of optically active anti-inflammatory 2-arylpropionic acids using (+)- or (−)-amphetamine as derivatizing reagent. J Chromatogr. 1986; 378: 125–35.PubMedCrossRefGoogle Scholar
  23. 23.
    Dusci LJ, Hackett LP. Determination of some anti-inflammatory drugs in serum by high-performance liquid chromatography. J Chromatogr. 1979; 172: 516–9.PubMedCrossRefGoogle Scholar
  24. 24.
    Pitrè D, Grandi M. Rapid determination of ibuprofen in plasma by high-performance liquid chromatography. J Chromatogr. 1979; 170: 278–81.PubMedCrossRefGoogle Scholar
  25. 25.
    Runci FM, Segre G. Gas Chromatographic determination of ibuprofen in plasma and in biological fluids. Chromatogr Symp Ser. 1979; 1: 199–201.Google Scholar
  26. 26.
    Orzalesi G, Mari F, Bertol E, et al. Anti-inflammatory agents: determination of ibuproxam and its metabolite in humans. Arzneimittel Forschung. 1980; 30: 1607–9.PubMedGoogle Scholar
  27. 27.
    Ali A, Kazmi S, Plakogiannis FM. High-pressure liquid Chromatographic determination of ibuprofen in plasma. J Pharm Sci. 1981; 70: 944–5.PubMedCrossRefGoogle Scholar
  28. 28.
    Kearns GL, Wilson JT. Determination of ibuprofen in serum by high-performance liquid chromatography and application to ibuprofen disposition. J Chromatogr. 1981; 226: 183–90.PubMedCrossRefGoogle Scholar
  29. 29.
    Shimek JL, Rao NGS, Khalil SK. High-pressure liquid Chromatographie determination of ibuprofen in plasma. J Pharm Sci. 1981; 70: 514–6.PubMedCrossRefGoogle Scholar
  30. 30.
    Snider BG, Beaubien LJ, Sears DJ, et al. Determination of flurbiprofen and ibuprofen in dog serum with automated sample preparation. J Pharm Sci. 1981; 70: 1347–9.PubMedCrossRefGoogle Scholar
  31. 31.
    Lockwood GF, Wagner JG. High-performance liquid Chromatographie determination of ibuprofen and its major metabolites in biological fluids. J Chromatogr. 1982; 232: 335–43.PubMedCrossRefGoogle Scholar
  32. 32.
    Aarons L, Grennan DM, Siddiqui M. The binding of ibuprofen to plasma proteins. Eur J Clin Pharmacol. 1983; 25: 815–8.PubMedCrossRefGoogle Scholar
  33. 33.
    Ford B, Vine J, Watson TR. A rapid extraction method for acidic drugs in hemolyzed blood. J Anal Toxicol. 1983; 7: 116–8.PubMedGoogle Scholar
  34. 34.
    Hirai T, Matsumoto S, Kishi I. Simultaneous analysis of several non-steroidal anti-inflammatory drugs in urine by high-performance liquid chromatography with normal-phase extraction. J Chromatogr B 1997; 375–88.Google Scholar
  35. 35.
    Greenblatt DJ, Arendt RM, Locniskar A. Ibuprofen pharmacokinetics: use of liquid chromatography with radial compression separation. Arzneimittel Forschung. 1983; 33: 1671–3.PubMedGoogle Scholar
  36. 36.
    Senekjian HO, Leee CS, Kuo TH, et al. Absorption and disposition of ibuprofen in hemodialyzed uremic patients. Eur J Rheumatol Inflamm. 1983; 6: 155–62.PubMedGoogle Scholar
  37. 37.
    Heikkinen L. Quantitative determination of ibuprofen by glass capillary gas chromatography using three different methylation methods. Acta Pharm Fenn. 1983; 92: 275–82.Google Scholar
  38. 38.
    Albert KS, Raabe A, Garry M, et al. Determination of ibuprofen in capillary and venous plasma by high-performance liquid chromatography with ultraviolet detection. J Pharm Sci. 1984; 73: 1487–9.PubMedCrossRefGoogle Scholar
  39. 39.
    Aravind MK, Miceli JN, Kauffman RE. Determination of ibuprofen by high-performance liquid chromatography. J Chormatogr. 1984; 308: 350–3.CrossRefGoogle Scholar
  40. 40.
    Heikkinen L. Silica caplillary gas Chromatographic determination of ibuprofen in serum. J Chromatogr. 1984; 307: 206–9.PubMedCrossRefGoogle Scholar
  41. 41.
    Litowitz H, Olanoff L, Hoppel CL. Determination of ibuprofen in human plasma by high-performance liquid chromatography. J Chromatogr. 1984; 311: 443–8.PubMedCrossRefGoogle Scholar
  42. 42.
    Chan EM, Chan SC. Screening for acidic and neutral drugs by high performance liquid chromatography in post-mortem blood. J Anal Toxicol. 1984; 8: 173–6.PubMedGoogle Scholar
  43. 43.
    Ginman R, Karnes HT, Perrin J. Simultaneous determination of codeine and ibuprofen by high-performance liquid chromatography. J Pharm Biomed Anal. 1985; 3: 439–45.PubMedCrossRefGoogle Scholar
  44. 44.
    Jonkman HG, Schoenmaker R, Holtkamp AH, et al. Determination of ibuprofen in human plasma by solid phase extraction and reversed-phase high-performance liquid chromatography. J Pharm Biomed Anal. 1985; 3: 433–8.PubMedCrossRefGoogle Scholar
  45. 45.
    Giachetti C, Canali S, Zanolo G. Separation of non-steroidal anti-inflammatory agents by high-resolution gas chromatography. Preliminary trials to perform pharmacokinetic studies. J Chromatogr. 1983; 279: 587–92.Google Scholar
  46. 46.
    Levine B, Caplan YH. Simultaneous liquid-chromatographic determination of five nonsteroidal anti-inflammatory drugs in plasma or blood. Clin Chem. 1985; 31: 346–47.PubMedGoogle Scholar
  47. 47.
    Shah A, Jung D. Improved high-performance liquid Chromatographie assay of ibuprofen in plasma. J Chormatogr. 1985; 344: 408–11.CrossRefGoogle Scholar
  48. 48.
    Lee EJD, Williams KM, Graham GG, et al. Liquid Chromatographie determination and plasma concentration profile of optical isomers of ibuprofen in humans. J Pharm Sci. 1984; 73: 1542–4.PubMedCrossRefGoogle Scholar
  49. 49.
    Averginos A, Hutt AJ. High-performance liquid Chromatographie determination of ibuprofen in human plasma and urine by direct injection. J Chromatogr. 1986; 380: 468–71.CrossRefGoogle Scholar
  50. 50.
    LaLande M, Wilson DL, MCGilveray IJ. Rapid high-performance liquid Chromatographic determination of ibuprofen in human plasma. J Chromatogr. 1986; 377: 410–4.PubMedCrossRefGoogle Scholar
  51. 51.
    Omile CI, Tebett IR. Determination of ten anti-inflammatory drugs in serum by isocratic liquid chromatography. Chromatographia. 1986; 22: 1–6.CrossRefGoogle Scholar
  52. 52.
    Young MA, Aarons L, Davidson EM, et al. Stereospecific assay of ibuprofen and its metabolites [abstract]. J Pharm Pharmacol. 1986; 38: 60.CrossRefGoogle Scholar
  53. 53.
    Kaluzny BD, Bannow CA. High-performance liquid Chromatographie determination of pimeprofen and its metabolite ibuprofen in sheep plasma and lymph. J Chromatogr. 1987; 414: 228–34.PubMedCrossRefGoogle Scholar
  54. 54.
    Moore CM, Tebbett IR. Rapid extraction of anti-inflammatory drugs in whole blood for HPLC analysis. Forsenic Sci Int. 1987; 34: 155–8.CrossRefGoogle Scholar
  55. 55.
    Owen SG, Roberts MS, Freisen WT. Rapid high-performance liquid Chromatographic assay for the simultaneous analysis of non-steroidal anti-inflammatory drugs in plasma. J Chromatogr. 1987; 416: 293–302.PubMedCrossRefGoogle Scholar
  56. 56.
    Chai B, Minkler PE, Hoppel CI. Determination of ibuprofen and its major metabolites in human urine by high-performance liquid chromatography. J Chromatogr. 1988; 430: 93–101.PubMedCrossRefGoogle Scholar
  57. 57.
    Karnes HT, Rajasekharaiah K, Small RE, et al. Automated solid phase extraction and HPLC analysis of ibuprofen in plasma. J Liq Chromatogr. 1988; 11: 489–9.CrossRefGoogle Scholar
  58. 58.
    Berner G, Engels B, Vogtle-Junkert U. Percutaneous ibuprofen therapy with trauma-dolgit gel: bioequivalence studies. Drugs Expt Clin Res. 1989; 15: 559–64.Google Scholar
  59. 59.
    Lapique F, Netter P, Bannwarth B, et al. Identification and simultantaneous determination of non-steroidal anti-inflammatory drugs using high-performance liquid chromatography. J Chromatogr. 1989; 496: 301–20.CrossRefGoogle Scholar
  60. 60.
    Satterwhite JH, Boudinot FD. High-performance liquid Chromatographic determination of ibuprofen in rat and human plasma. J Chromatogr. 1989; 497: 330–5.PubMedCrossRefGoogle Scholar
  61. 61.
    Schulz M, Schmoldt A. Determination of nonsteroidal anti-inflammatory drugs in human plasma by high-performance liquid chromatography. Pharm Ztg Wiss. 1989; 134: 41–4.Google Scholar
  62. 62.
    Streete PJ. Rapid high-performance liquid Chromatographic methods for the determination of some non-steroidal anti-inflammatory drugs in plasma or serum. J Chromatogr. 1989; 495: 179–93.PubMedCrossRefGoogle Scholar
  63. 63.
    Berner G, Staab R, Wagener HH. Determination of ibuprofen in plasma, synovial fluid and tissue by HPLC with electrochemical detection in the lower ng-range. Fresenius J Anal Chem. 1990; 336: 238.CrossRefGoogle Scholar
  64. 64.
    Marzo A, Reiner A, Monti N, et al. Evaluation of ibuprofen dimethylaminoethanol octyl bromide and related active metabolites in biological samples. Arzneimittel Forschung. 1990; 40: 614–7.PubMedGoogle Scholar
  65. 65.
    Rustum AM. Measurement of ibuprofen in human whole blood by reversed-phase ion-paired high-performance liquid chromatography using a pH-stable polymeric column. J Chromatogr. 1990; 526: 246–53.PubMedCrossRefGoogle Scholar
  66. 66.
    Nahata MC. Determination of ibuprofen in human plasma by high-performance liquid chromatography. J Liq Chromatogr. 1991; 14: 187–92.CrossRefGoogle Scholar
  67. 67.
    Rustum AM. Assay of ibuprofen in human plasma by rapid and sensitive reversed-phase high-performance liquid chromaography: application to a single dose pharmacokinetic study. J Chromatogr Sci. 1991; 29: 16–20.PubMedGoogle Scholar
  68. 68.
    Yamashita K, Motohashi M, Yashiki T. Column-switching techniques for high-performance liquid chromatography of ibuprofen and mefenamic acid in human serum with short-wavelength ultraviolet detection. J Chromatogr. 1991; 570: 329–38.PubMedCrossRefGoogle Scholar
  69. 69.
    Blagbrough IS, Daykin MM, Doherty M, et al. PN. High-performance liquid Chromatographic determination of diclofenac, ibuprofen and diclofenac in plasma and synovial fluid in man. J Chromatogr. 1992; 578: 251–7.PubMedCrossRefGoogle Scholar
  70. 70.
    Jack DS, Rumble RH, Davies NW, et al. Enantiospecific gas chromatographic-mass spectrometric procedure for the determination of ketoprofen and ibuprofen in synovial fluid and plasma: application to protein binding studies. J Chromatogr. 1992; 584: 189–97.PubMedCrossRefGoogle Scholar
  71. 71.
    Jung ES, Lee HS, Rho JK et al. Simultaneous determination of ibuproxam and ibuprofen in human plasma by HPLC with column switching. Chromatographia. 1993; 37: 618–22.CrossRefGoogle Scholar
  72. 72.
    Zhao M-J, Peter C, Holtz M-C, et al. Gas chromatographic-mass spectrometric determination of ibuprofen enantiomers in human plasma using R(−)-2,2,2-trifluoro-1-(9-anthryl)ethanol as derivatizing reagent. J Chromatogr. 1994; 656: 441–6.CrossRefGoogle Scholar
  73. 73.
    Steijger OM, Lingeman H, Brinkman UAT, et al. Liquid Chromatographic analysis of carboxylic acids uszng N-(4-aminobutyl)-N-ethylisoluminol as chemiluminescent label: determination of ibuprofen in saliva. J Chromatogr. 1993; 615: 97–110.PubMedCrossRefGoogle Scholar
  74. 74.
    Kim K-R, Shim W-H, Shin Y-J, et al. Capillary gas chromatography of acidic non-steroidal antiinflammatory drugs as tertbutyldimethylsilyl derivatives. J Chromatogr. 1993; 641: 319–27.CrossRefGoogle Scholar
  75. 75.
    Rifai N, Sakamoto M, Law T, et al. Use of a rapid HPLC assay for determination of pharmacokinetic parameters of ibuprofen in patients with cystic fibrosis. Clin Chem. 1994; 42: 1812–6.Google Scholar
  76. 76.
    Wilson WH. Direct enantiomeric resolution of ibuprofen and flurbiprofen by packed column SFC. Chirality. 1994; 6: 216–9.CrossRefGoogle Scholar
  77. 77.
    Kim K-R, Shin Y-J, Shim W-H, et al. Rapid gas Chromatographie profiling and screening of acidic non-steroidal anti-inflammatory drugs in biological samples. Arch Pharm Res. 1994; 17: 175–81.CrossRefGoogle Scholar
  78. 78.
    Vangiessen GJ, Kaiser DG. GLC determination of ibuprofen [dl-2-(p-isobutylphenyl)propionic acid] enantiomers in biological specimens. J Pharm Sci. 1975; 64: 798–801.PubMedCrossRefGoogle Scholar
  79. 79.
    Crowther JB, Covey TR, Dewey EA, et al. Liquid chromatographic/mass spectrometric determination of optically active drugs. Anal Chem. 1984; 56: 2921–6.PubMedCrossRefGoogle Scholar
  80. 80.
    Giachetti C, Zanolo G, Canali S. Topical administration of ibuprofen in man: simultaneous determination of the drug and its metabolites in urine by high resolution gas chromatography. J High Res Chromatogr Commun. 1985; 8: 465–8.CrossRefGoogle Scholar
  81. 81.
    Whitlam JB, Vine JH. Quantitation of ibuprofen in biological fluids by gas chromatography-mass spectrometry. J Chromatogr. 1980; 181: 463–8.PubMedCrossRefGoogle Scholar
  82. 82.
    Averginos A, Hutt AJ. Determination of the enantiomeric composition of ibuprofen in human plasma by high-performance liquid chromatography. J Chromatogr. 1987; 415: 75–83.CrossRefGoogle Scholar
  83. 83.
    Minkler PE, Hoppel CL. Determination of ibuprofen in human plasma by high-perfomance liquid chromatography. J Chromatogr. 1988; 428: 388–94.PubMedCrossRefGoogle Scholar
  84. 84.
    Nicoll-Griffith DA, Inaba T, Tang BK, et al. Method to determine the enantiomers of ibuprofen from humna urine by high-performance liquid chromatography. J Chromatogr. 1988; 428: 103–12.PubMedCrossRefGoogle Scholar
  85. 85.
    Mehvar R, Jamali F, Pasutto FM. Liquid-chromatographic assay of ibuprofen enantiomers in plasma. Clin Chem. 1988; 34: 493–6.PubMedGoogle Scholar
  86. 86.
    Geisslinger G, Dietzel K. High-performance liquid Chromatographie determination of ibuprofen, its metabolites and enantiomers in biological fluids. J Chromatogr. 1989; 491: 139–49.PubMedCrossRefGoogle Scholar
  87. 87.
    Martin W, Koselowske G, Toberich H, et al. Pharmacokinetics and absolute bioavailability of ibuprofen after oral administration of ibuprofen lysine in man. Biopharm Drug Disp. 1990; 11: 265–78.CrossRefGoogle Scholar
  88. 88.
    Menzel-Soglowek S, Geisslinger G, Brune K. Stereoselective high-performance liquidchromatographic determination of ketoprofen, ibuprofen and fenoprofen in plasma using a chiral α1-acid glycoprotein column. J Chromatogr. 1990; 532: 295–303.PubMedCrossRefGoogle Scholar
  89. 89.
    Pettersson K-J, Olsson A. Liquid Chromatographic determination of the enantiomers of ibuprofen in plasma using a chiral AGP column. J Chromatogr. 1991; 563: 414–8.PubMedCrossRefGoogle Scholar
  90. 90.
    Theis DL, Halstead GW, Halm KA. Development of capillary gas chromaotgraphic-mass spectrometric methodology for the simultaneous determination of ibuprofen and [ar-2H4] ibuprofen in serum: demonstration of kinetic equivalence in the beagle. J Chromatogr. 1986; 380: 77–87.PubMedCrossRefGoogle Scholar
  91. 91.
    Wright MR, Sattari S, Brocks DR, et al. Improved high-performance liquid Chromatographic assay method for the enantiomers of ibuprofen. J Chromatogr. 1992; 583: 259–65.PubMedCrossRefGoogle Scholar
  92. 92.
    Lemko CH, Caillé G, Foster RT. Stereospecific high-performance liquid Chromatographic assay of ibuprofen: improved sensitivity and sample processing efficiency. J Chromatogr. 1993; 619: 330–5.PubMedCrossRefGoogle Scholar
  93. 93.
    Ahn H-Y, Shiu GK, Trafton WF, et al. Resolution of the enantiomers of ibuprofen; comparison study of diastereomeric method and chiral stationary phase method. J Chromatogr B. 1994; 653: 163–9.CrossRefGoogle Scholar
  94. 94.
    De Vries JX, Schmitz-Kummer E, Siemon D. The analysis of ibuprofen enantiomers in human plasma and urine by high-performance liquid chromatography on an α1-acid glycoprotein chiral stationary phase. J Liq Chromatogr. 1994; 17: 2127–45.CrossRefGoogle Scholar
  95. 95.
    Kondo J, Suzuki N, Naganuma H, et al. Enantiospecific determination of ibuprofen in rat plasma using chiral fluorescence derivatization reagent, (−)-2-[4-(1-aminoethyl)-phenyl]-6-methoxybenzoxazole. Biomed Chromatogr. 1994; 8: 170–4.PubMedCrossRefGoogle Scholar
  96. 96.
    Naidong W, Lee JW. Development and validation of a liquid Chromatographic method for the qunatitation of ibuprofen enantiomers in human plasma. J Pharm Biomed Anal. 1994; 12: 551–6.PubMedCrossRefGoogle Scholar
  97. 97.
    Kunsman GW, Rohrig TP. Tissue distribution of ibuprofen in a fatal overdose. Am J Forensic Med Pathol. 1993; 14: 48–50.PubMedCrossRefGoogle Scholar
  98. 98.
    Péhourcq F, Lagrange F, Labat L, et al. Simultaneous measurement of flurbiprofen, ibuprofen, and ketoprofen enantiomer concentrations in plasma using L-leucinamide as the chiral coupling component. J Liq Chromatorgr. 1995; 18: 3969–79.CrossRefGoogle Scholar
  99. 99.
    Gabard B, Nirnberger G, Schiel H, et al. Comparison of the bioavailability of dexibuprofen administered alone or as part of racemic ibuprofen. Eur J Clin Pharmacol. 1995; 48: 505–11.PubMedCrossRefGoogle Scholar
  100. 100.
    Lau YY. Determination of ibuprofen enantiomers in human plasma by derivatization and high performance liquid chromatography with fluoresence detection. J Liq Chromatogr Rel Technol. 1996; 19: 2143–53.CrossRefGoogle Scholar
  101. 101.
    Terfloth GJ, Pirkle WH, Lynam KG, et al. Broadly applicable polysiloxane-based chiral stationary phase for high-performance liquid chromatography and supercritical fluid chromatography. J Chromatogr. 1995; 705: 185–94.CrossRefGoogle Scholar
  102. 102.
    Suzuki N, Naganuma H, Kondo J, et al. Enantiospecific determination of ibuprofen in rat plasma using chiral fluorescence derivatization reagent, (−)-2-[4-(1-Aminoethyl)phenyl]-6-methoxybenzoxazole [abstract]. Int Symp Mol Chir. 1994; 524: 314.Google Scholar
  103. 103.
    Askholt J, Nielsen-Kudsk F. Rapid HPLC-Determination of ibuprofen and flurbiprofen in plasma for therapeutic drug control and pharmacokinetic applications. Acta Pharmacol Toxicol. 1986; 59: 282–6.Google Scholar
  104. 104.
    Sochor J, Klimes J, Zahradnicke M, et al. High-Performance liquid chromaotgraphic assay for ibuprofen in whole blood using soli-phase extraction. J Chromatogr. 1994; 654: 282–6.CrossRefGoogle Scholar
  105. 105.
    Brooks CJW, Gilbert MT. Studies of urinary metabolites of 2-(4-isobutylphenyl)propionic acid by gas-liquid chromatography-mass spectrometry. J Chromatogr. 1974; 99: 541–51.PubMedCrossRefGoogle Scholar
  106. 106.
    Maurer HH, Kraemer T, Weber A. Toxicological detection of ibuprofen and its metabolites in urine using gas chromatography-mass spectrometry (GC-MS). Pharmazie. 1994; 49: 148–50.PubMedGoogle Scholar
  107. 107.
    Save TK, Parmar DV, Devarajan PV. High-performance thinlayer Chromatographic determination of ibuprofen in plasma. J Chromatogr. 1997; 690: 315–9.CrossRefGoogle Scholar
  108. 108.
    Davies NM. Methods of analysis of chiral non-steroidal anti-inflammatory drugs. J Chromatogr B. 1997; 691: 229–62.CrossRefGoogle Scholar
  109. 109.
    D’Hulst A, Verbeke N. Chiral separation by capillary electrophoresis with oligosaccharides. J Chromatogr. 1992; 608: 275–87.PubMedCrossRefGoogle Scholar
  110. 110.
    Maboundou CW, Paintaud G, Berard M, et al. Separation of fifteen non-steroidal anti-inflammatory drugs using micellar electrokinetic capillary chromatography. J Chromatogr B. 1994; 657: 173–83.CrossRefGoogle Scholar
  111. 111.
    Petersson P, Markides KE. Chiral separations performed by supercritical fluid chromatography. J Chromatogr. 1994; 666: 381–94.CrossRefGoogle Scholar
  112. 112.
    Shihabi ZK, Hinsdale ME. Analysis of ibuprofen in serum by capillary electrophoresis. J Chromatogr. 1996; 683: 115–8.CrossRefGoogle Scholar
  113. 113.
    Bhushan R, Parshad V. Resolution of (±)-ibuprofen using L-arginine-impregnated thin-layer chromatography. J Chromatogr. 1996; 721: 369–72.CrossRefGoogle Scholar
  114. 114.
    Toyo’oka T, Ishibashi M, Terao T. Resolution of carboxylic acid enantiomers by high-performance liquid chromaogrpahy with peroxylate chemiluminescence. J Chromatogr. 1997; 627: 75–86.Google Scholar
  115. 115.
    Mills RFN, Adams SS, Cliffe EE, et al. The metabolism of ibuprofen. Xenobiotica. 1973; 9: 589–98.CrossRefGoogle Scholar
  116. 116.
    Collier PS, D’Arcy PF, Harron DWG, et al. Pharmacokinetic modelling of ibuprofen. Br J Clin Pharmacol. 1978; 5: 528–30.PubMedCrossRefGoogle Scholar
  117. 117.
    Mäkelä A-L, Lempiäinen M, Yrjänä T. Ibuprofen in the treatment of juvenile rheumatoid arthritis: metabolism and concentrations in synovial fluid. Br J Clin Pract. 1980; 6: 23–7.Google Scholar
  118. 118.
    Mäkelä A-L, Lempiäinen M, Ylijoki H. Ibuprofen levels in serum and synovial fluid. Scand J Rheumatol. 1981; 39: 15–7.CrossRefGoogle Scholar
  119. 119.
    Barillari G, Iorio E, Catanese B, et al. A study of the absorption and tolerance of ibuprofen guaiacol ester in man after repeated oral administration. Boll Chim Farm. 1982; 121: 626–31.PubMedGoogle Scholar
  120. 120.
    Catanese B, Barillari G, Iorio E, et al. Studies on the oral absorption of ibuprofen guaiacol-ester in man. Boll Chim Farm. 1982; 121: 567–72.PubMedGoogle Scholar
  121. 121.
    Gillespie WR, DiSanto AR, Monovich RE, et al. Relative bioavailability of commercially available ibuprofen oral dosage forms in humans. J Pharm Sci. 1982; 71: 1034–8.PubMedCrossRefGoogle Scholar
  122. 122.
    Zanola G, Mondino A, Giachetti G, et al. Humankinetische Untersuchungen mit ibuprofen. Therapiewoche. 1982; 32: 4353–7.Google Scholar
  123. 123.
    Aarons L, Greenan DM, Rajapakse C, et al. Anti-inflammatory (ibuprofen) drug therapy in rheumatoid arthritis: rate of response and lack of time dependency of plasma pharmacokinetics. Br J Clin Pharmac. 1983; 15: 387–8.CrossRefGoogle Scholar
  124. 124.
    Juhl RP, Van Thiel DH, Dittert LW, et al. Ibuprofen and sulindac kinetics in alcoholic liver disease. Clin Pharmacol Ther. 1983; 34: 104–9.PubMedCrossRefGoogle Scholar
  125. 125.
    Lockwood GF, Albert KS, Gillespie WR, et al. Pharmacokinetics of ibuprofen in man. 1: free and total area/dose relationships. Clin Pharmacol Ther. 1983; 31: 97–103.Google Scholar
  126. 126.
    Stead JA, Freeman M, John EG, et al. Ibuprofen tablets: dissolution and bioavailability studies. Int J Pharm. 1983; 14: 59–72.CrossRefGoogle Scholar
  127. 127.
    Wright CE, Antal EJ, Gillespie WR, et al. Ibuprofen and acetaminophen kinetics when taken concurrently. Clin Pharmacol Ther. 1983; 34(5): 707–10.PubMedCrossRefGoogle Scholar
  128. 128.
    Zanola G, Mondino A, Giachetti G, et al. Ibuprofen-serumkonzentration nach oraler applikation von Dolgit® retard. Therapiewoche. 1983; 33: 2114–6.Google Scholar
  129. 129.
    Albert KS, Gillespie WR, Wagner JG, et al. Effects of age on the clinical pharmacokinetics of ibuprofen. Am J Med. 1984; 6: 47–50.CrossRefGoogle Scholar
  130. 130.
    Pugh MC, Small RE, Garnett WR, et al. Effect of sucralfate on ibuprofen absorption in normal volunteers. Clin Pharm. 1984; 3: 630–3.PubMedGoogle Scholar
  131. 131.
    Greenblatt DJ, Abernathy DR, Methis R, et al. Absorption and disposition of ibuprofen in the elderly. Arthritis Rheum. 1984; 27: 1066–9.PubMedCrossRefGoogle Scholar
  132. 132.
    Abernathy DR, Greenblatt DJ. Ibuprofen disposition in obese individuals. Arthritis Rheum. 1985; 28: 1117–21.CrossRefGoogle Scholar
  133. 133.
    Gambaro V, Caligara M, Benvenuti C, et al. Pharmacokinetics of ibuprofen microincapsulated granules. II Farmaco. 1985; 40: 407–15.Google Scholar
  134. 134.
    Ochs HR, Greenblatt DJ, Matlis R, et al. Interaction of ibuprofen with the H-2 receptor antagonists ranitidine and cimetidine. Clin Pharmacol Ther. 1985; 38: 648–51.PubMedCrossRefGoogle Scholar
  135. 135.
    Palva ES, Konno K, Venbo VMK. Bioavailability of ibuprofen from three preparations marketed in Finland. Acta Pharm Fenn. 1985; 94: 31–5.Google Scholar
  136. 136.
    Anaya AL, Mayersohn M, Conrad KA, et al. The influence of sucralfate on ibuprofen absorption in healthy adult males. Biopharm Drug Disp. 1986; 7: 433–51.CrossRefGoogle Scholar
  137. 137.
    Antal EJ, Wright CE, Brown BL, et al. The influence of hemodialysis on the pharmacokinetics of ibuprofen and its major metabolites. J Clin Pharmacol. 1986; 26: 184–90.PubMedGoogle Scholar
  138. 138.
    Benvenuti C, Cancellieri V, Gambaro V, et al. Pharmacokinetics of two new oral formulations of ibuprofen. In J Clin Pharmacol Toxicol. 1986; 24: 308–12.Google Scholar
  139. 139.
    Gallo JM, Gall EP, Gillespie WR, et al. Ibuprofen kinetics in plasma and synovial fluid arthritic patients. J Clin Pharmacol. 1986; 26: 65–70.PubMedGoogle Scholar
  140. 140.
    Müller FO, Hundt HK, Van Dyk M, et al. Ibuprofen bioavailability: a comparison of brufen and inza. S Afr Med J. 1986; 70: 197–9.PubMedGoogle Scholar
  141. 141.
    Regazzi BM, Rondanelli R, Ciaroelli L, et al. Evaluation of the absorption from three formulations. Int Clin Pharm Res. 1986; 6: 469–73.Google Scholar
  142. 142.
    Gontarz N, Small RE, Comstock TJ, et al. Effect of antacid suspension on the pharmacokinetics of ibuprofen. Clin Pharm. 1987; 6: 413–6.PubMedGoogle Scholar
  143. 143.
    Lau L-B, Feing-Fei M, Xi-De T. Studies on the bioavailability of ibuprofen tablets. Acta Pharm Sin. 1987; 22: 769–76.Google Scholar
  144. 144.
    Parr AF, Beihn RM, Franz RM, et al. Correlation of ibuprofen bioavailability with gastrointestinal transit by scintigraphic monitoring of 171Er-labeled sustained-release tablets. Pharm Res. 1987; 4: 486–9.PubMedCrossRefGoogle Scholar
  145. 145.
    Berardi RR, Dressman JB, Elta GH, et al. Elevation of gastric pH with ranitidine does not affect the release characterisitcs of sustained release ibuprofen tablets. Biopharm Drug Disp. 1988; 9: 337–47.CrossRefGoogle Scholar
  146. 146.
    Forsyth DR, Jayasinghe KSA, Roberts CJC. Do nizatidine and cimetidine interact with ibuprofen? Eur J Clin Pharmacol. 1988; 35: 85–8.PubMedCrossRefGoogle Scholar
  147. 147.
    Källström E, Heikinheimo M, Quiding H. Bioavailability of three commericial preparations of ibuprofen 600mg. J Int Med Res. 1988; 16: 44–9.PubMedGoogle Scholar
  148. 148.
    Small RE, Johnson SM, Willis HE. Pharmacokinetic and taste evaluation of ibuprofen (Motrin®) 800mg tablets in extemporaneous solution. J Rheumatol. 1988; 15: 345–7.PubMedGoogle Scholar
  149. 149.
    Stephenson DW, Small RE, Wood JH, et al. Effect of rantitidine and cimetidine on ibuprofen pharmacokinetics. Clin Pharm. 1988; 7: 317–21.PubMedGoogle Scholar
  150. 150.
    Eller MG, Wright C, Della-Coletta AA. Absorption kinetics of rectally and orally administered ibuprofen. Biopharm Drug Disp. 1989; 10: 269–78.CrossRefGoogle Scholar
  151. 151.
    Sprekeler R, Baurecht W. Pharmakokinetische kennwerte unter therapie mit einem nichtsteroidalen antirheumatikum mit kurzer halbwertszeit bei patienten über 65 jahren. Arzneimittel Forschung. 1989; 39: 912–4.PubMedGoogle Scholar
  152. 152.
    Wilson CG, Washington N, Greaves JL, et al. Bimodal release of ibuprofen in a sustained-release formulation: a scintigraphic and pharmacokinetic open study in healthy volunteers under different conditions of food intake. Int J Pharm. 1989; 50: 155–61.CrossRefGoogle Scholar
  153. 153.
    Borin MT, Khare S, Beihn RM, et al. The effect of food on gastrointestinal (GI) transit of sustained-release ibuprofen tablets as evaluated by gamma scintigraphy. Pharm Res. 1990; 7: 304–7.PubMedCrossRefGoogle Scholar
  154. 154.
    Freidman H, Lanza F, Perry K, et al. Clinical pharmacology of predisintegrated ibuprofen 800mg tablets: an endoscopic and pharmacokinetic study. J Clin Pharmacol. 1990; 30: 57–63.Google Scholar
  155. 155.
    Hannula AM, Marvola M, Rajamaeki M, et al. Effects of pH regulators used as additives on the bioavailability of ibuprofen from hard gelatin capsules. Acta Pharm Fenn. 1990; 7: 221–7.Google Scholar
  156. 156.
    Karttunen P, Saano V, Paronen P, et al. Pharmacokinetics of ibuprofen in man: a single-dose comparison of two over-the-counter, 200mg preparations. Int J Clin Pharmacol Ther Toxicol. 1990; 28: 251–5.PubMedGoogle Scholar
  157. 157.
    Kendall MJ, Jubb R, Bird HA, et al. A pharmacokinetic comparison of ibuprofen sustained-release tablets given to young and elderly patients. J Clin Pharm Ther. 1990; 15: 35–40.PubMedCrossRefGoogle Scholar
  158. 158.
    Lenhard G, Kieferndorf U, Berner G, et al. Pharmacokinetik un bioäquivalenz von zwei ibuprofen-formulierungen. Arzneimittel Forschung. 1990; 40: 1358–62.PubMedGoogle Scholar
  159. 159.
    Konstan MW, Hoppel CL, Chai B-L, et al. Ibuprofen in children with cystic fibrosis: pharmacokinetics and adverse effects. J Pediatr. 1991; 118: 956–64.PubMedCrossRefGoogle Scholar
  160. 160.
    Nahata MC, Durrell DE, Powell DA, et al. Pharmacokinetics of ibuprofen in febrile children. Eur J Clin Pharmacol. 1991; 40: 427–8.PubMedCrossRefGoogle Scholar
  161. 161.
    Neuvonen PJ. The effect of magnesium hydroxide on the oral absorption of ibuprofen, ketoprofen and diclofenac. Br J Clin Pharmacol. 1991; 31: 263–6.PubMedCrossRefGoogle Scholar
  162. 162.
    Saano V, Paronen P, Peura P, et al. Relative pharmacokinetics of three oral 400mg ibuprofen dosage forms in healthy volunteers. In J Clin Pharm Ther Toxicol. 1991; 29: 381–5.Google Scholar
  163. 163.
    Salas-Herrera IG, Pearson RM, Turner P. Concentration of ibuprofen in cervical mucus. J Pharm Pharmacol. 1991; 43: 142–4.PubMedCrossRefGoogle Scholar
  164. 164.
    Small RE, Wilmot-Pater MG, McGee BA, et al. Effects of misoprostol or ranitidine on ibuprofen pharmacokinetics. Clin Pharm. 1991; 10: 870–2.PubMedGoogle Scholar
  165. 165.
    Brown RD, Wilson JT, Kearns GL, et al. Single-dose pharmacokinetics of ibuprofen and acetaminophen in febrile children. J Clin Pharmacol. 1992; 32: 231–41.PubMedGoogle Scholar
  166. 166.
    Ceppi Monti N, Gazzaniga A, Gianesello V, et al. Activity and pharmacokinetics of a new oral dosage form of soluble ibuprofen. Arzneimittel Forschung. 1992; 42: 556–9.PubMedGoogle Scholar
  167. 167.
    Chen M-L. An alternative approach for assessment of rate of absorption in bioequivalence studies. Pharm Res. 1992; 9: 1380–5.PubMedCrossRefGoogle Scholar
  168. 168.
    Kauffman RE, Nelson MV. Effect of age on ibuprofen pharmacokinetics and antipyretic response. J Pediatr. 1992; 121: 969–73.PubMedCrossRefGoogle Scholar
  169. 169.
    Kelley MT, Walson PD, Edge JH, et al. Pharmacokinetics and pharmacodynamics of ibuprofen isomers and acetaminophen in febrile children. Clin Pharmacol Ther. 1992; 52: 181–9.PubMedCrossRefGoogle Scholar
  170. 170.
    Luckow V, Krammer R, Traub R. Vergleichende bioverfugbarkeitsuntersuchung zweier versciedener ibuprofen-granulate. Arzneimittel Forschung. 1992; 42: 1339–42.PubMedGoogle Scholar
  171. 171.
    Ragni MV, Miller BJ, Whalen R, et al. Bleeding tendency, platelet function, and pharmacokinetics of ibuprofen and zidovudine in HTV(+) hemophilie men. Am J Hem. 1992; 40: 176–82.CrossRefGoogle Scholar
  172. 172.
    Cone JB, Wallace BH, Olsen KM, et al. The pharmacokinetics of ibuprofen after burn injury. J Burn Care Rehabil. 1993; 14: 666–9.PubMedCrossRefGoogle Scholar
  173. 173.
    Seth PL. Percutaneous absorption of ibuprofen from different fromulations: comparative study with gel, hydrophilic ointment and emulsion cream. Arzneimittel Forschung. 1993; 43: 919–21.PubMedGoogle Scholar
  174. 174.
    Al-Meshal MA, El-Sayed YM, Al-Balla SR, et al. The effect of colestipol and cholestyramine on ibuprofen bioavailability in man. Biopharm Drug Disp. 1994; 15: 463–71.CrossRefGoogle Scholar
  175. 175.
    Kaltenbach ML, Mohammed SS, Mullersman G, et al. Pharmacokinetic evaluation of two ibuprofen-codeine combinations. Int J Clin Pharmacol Ther. 1994; 32: 210–4.PubMedGoogle Scholar
  176. 176.
    Rey E, Pariente-Khayat A, Gouyet L, et al. Stereoselective dispostition of ibuprofen enantiomers in infants. Br J Clin Pharmac. 1994; 38: 373–5.CrossRefGoogle Scholar
  177. 177.
    El-Sayed YM, Gouda MW, Al-Khamis Kl, et al. Comparative bioavailability of two tablet formulations of ibuprofen. Int J Clin Pharmacol Ther. 1995; 33: 294–8.PubMedGoogle Scholar
  178. 178.
    Kleinbloesem CH, Owerkerk M, Spitznagel W, et al. Pharmacokinetics and bioavailability of percutaneous ibuprofen. Arzneimittel Forschung. 1995; 45: 1117–21.PubMedGoogle Scholar
  179. 179.
    Walter K, Weib G, Laicher A, et al. Pharmacokinetics of ibuprofen following a single administration of a suspension containing enteric-coated microcapsules. Arzneimittel Foschung. 1995; 45: 886–90.Google Scholar
  180. 180.
    Ntawukulilyayo JD, Veraet C, Remon JP, et al. In vitro and in vivo evaluation of a xanthan gum-n-octenylsuccinate starch matrix tablet containing ibuprofen as a model drug. Int J Pharm. 1996; 139: 79–85.CrossRefGoogle Scholar
  181. 181.
    Pargal A, Kelkar MG, Nayak PJ. The effect of food on the bioavailability of ibuprofen and flurbiprofen from sustained release formulations. Biopharm Drug Disp. 1996; 17: 511–9.CrossRefGoogle Scholar
  182. 182.
    Wagener HH, Vögtle-Junkert U. Zur auswertung von wirkstoffkonzentration in geweben nach perkutaner anwendung von nicht-steroidalen antirheumatika. Arzneimittel Forschung. 1996; 46: 299–301.PubMedGoogle Scholar
  183. 183.
    Aranda JV, Varvarigou A, Beharry K, et al. Pharmacokinetics and protein binding of intravenous ibuprofen in the premature newborn infant. Acta Paediatr. 1997; 86: 289–93.PubMedCrossRefGoogle Scholar
  184. 184.
    Jones K, Seymour RA, Hawkesford JE. Are the pharmacokinetics of ibuprofen important determinants for the dru’s efficacy in postoperative pain after third molar surgery? Br J Oral Maxillofac Surg. 1997; 35(3): 173–6.PubMedCrossRefGoogle Scholar
  185. 185.
    Lee EJD, Williams KM, Day RO, et al. Stereoselective disposition of ibuprofen enantiomers in man. Br J Clin Pharmacol. 1985; 19: 669–74.PubMedCrossRefGoogle Scholar
  186. 186.
    Cox SR, Brown MA, Squires DJ, et al. Comparative human study of ibuprofen enantiomer plasma concentrations produced by two commercially available ibuprofen tablets. Biopharm Drug Disp. 1988; 9: 539–49.CrossRefGoogle Scholar
  187. 187.
    Day RO, Williams KM, Graham GG, et al. Stereoselective disposition of ibuprofen enantiomers in synovial fluid. Clin Pharmacol Ther. 1988; 43: 480–7.PubMedCrossRefGoogle Scholar
  188. 188.
    Jamali F, Singh NN, Pasutto FM, et al. Pharmacokinetics of ibuprofen enantiomers in man following oral administration of tablets with different absorption rates. Pharm Res. 1988; 5: 40–3.PubMedCrossRefGoogle Scholar
  189. 189.
    Evans AM, Nation RL, Sansom LN. Lack of effect of cimetidine on the pharmacokinetics of R(−)- and S(+)-ibuprofen. Br J Clin Pharmacol. 1989; 28: 143–9.PubMedCrossRefGoogle Scholar
  190. 190.
    Baillie TA, Adams WJ, Kaiser DG, et al. Mechanistic studies of the metabolic chiral inversion of (R)-ibuprofen in humans. J Pharm Exp Ther. 1989; 249: 517–23.Google Scholar
  191. 191.
    Li G, Treiber G, Klotz U. The ibuprofen-cimetidine interaction stereochemical considerations. Drug Invest. 1989; 1: 11–7.Google Scholar
  192. 192.
    Averginos A, Hutt AJ. Interindividual variability in the enantiomeric disposition of ibuprofen follwing the oral administration of the racemic drug to healthy volunteers. Chirality. 1990; 2: 249–56.CrossRefGoogle Scholar
  193. 193.
    Evans AM, Nation RI, Sansom LN, et al. The relationship between the pharmacokinetics of ibuprofen enantiomers and the dose of racemic ibuprofen in humans. Biopharm Drug Dispos. 1990; 2: 507–18.CrossRefGoogle Scholar
  194. 194.
    Geisslinger G, Schuster O, Stock KP, et al. Pharmacokinetics of S(+)- and R(−)-ibuprofen in volunteers and first clinical experience of S(+)-ibuprofen in rheumatoid arthritis. Eur J Clin Pharmacol. 1990; 38: 493–7.PubMedCrossRefGoogle Scholar
  195. 195.
    Cox SR, Gall EP, Forbes KK, et al. Pharmacokinetics of the R (−) and S(+) enantiomers of ibuprofen in the serum and synovial fluid of arthritic patients. J Clin Pharmacol. 1991; 31: 88–94.PubMedGoogle Scholar
  196. 196.
    Wagener HH, Kalbhen DA, Berner G, et al. Ibuprofen-racemate und enantiomere. Akt Rheumatol. 1991; 16: 65–9.CrossRefGoogle Scholar
  197. 197.
    Jamali F, Mehvar R, Russell AS, et al. Human pharmacokinetics of ibuprofen enantiomers following different doses and formulations: intestinal chiral inversion. J Pharm Sci. 1992; 81: 221–5.PubMedCrossRefGoogle Scholar
  198. 198.
    Levine MAH, Walker SE, Paton TW. The effect of food or sucralfate on the bioavailability of S (+) and R(−) enantiomers of ibuprofen. J Clin Pharmacol. 1992; 32: 1110–4.PubMedGoogle Scholar
  199. 199.
    Oliary J, Tod M, Nicolas P, et al. Pharmacokinetics of ibuprofen enantiomers after single and repeated doses in man. Biopharm Drug Disp. 1992; 13: 337–44.CrossRefGoogle Scholar
  200. 200.
    Rudy AC, Bradley JD, Ryan SI, et al. Variability in the disposition of ibuprofen enantiomers in osteoarthritic patients. Ther Drug Monitor. 1992; 14: 464–70.CrossRefGoogle Scholar
  201. 201.
    Hall SD, Rudy AC, Knight PM, et al. Lack of presystemic inversion of (R)- to (S)-ibuprofen in humans. Clin Pharmacol Ther. 1993; 53: 393–400.PubMedCrossRefGoogle Scholar
  202. 202.
    Geisslinger G, Stock KP, Loew D, et al. Variability in the stereoselective disposition of ibuprofen in patients with rheumatoid arthritis. Br J Clin Pharmacol. 1993; 35: 603–7.PubMedCrossRefGoogle Scholar
  203. 203.
    Li G, Treiber G, Maier K, et al. Disposition of ibuprofen in patients with liver cirrhosis: stereochemical considerations. Clin Pharmacokinet. 1993; 25: 154–63.PubMedCrossRefGoogle Scholar
  204. 204.
    Walker JS, Knihinicki RD, Seideman P, et al. Pharmacokinetics of ibuprofen enantiomers in plasma and suction blister fluid in healthy volunteers. J Pharm Sci. 1993; 82: 787–90.PubMedCrossRefGoogle Scholar
  205. 205.
    Chen C-Y, Chen C-S. Stereoselective disposition of ibuprofen in patients with renal dysfunction. J Pharm Exp Ther. 1994; 258: 590–4.Google Scholar
  206. 206.
    Smith DE, Paliwal JK, Cox SR, et al. The effect of competitive and non-linear plasma protein binding on the stereoselective disposition and metabolic inversion of ibuprofen in healthy subjects. Biopharm Drug Disp. 1994; 15: 545–61.CrossRefGoogle Scholar
  207. 207.
    Bannwarth B, Lapique F, Pehourq F, et al. Stereoselective disposition of ibuprofen enantiomers in human cerebrospinal fluid. Br J Clin Pharmacol. 1995; 40: 266–9.PubMedCrossRefGoogle Scholar
  208. 208.
    Chen C-Y. Influence of age on the stereoselective disposition and metabolism of ibuprofen in humans. J Formos Med Assoc. 1995; 94: 95–100.PubMedGoogle Scholar
  209. 209.
    Chen C-Y, Chen C-S. Stereoselective disposition of ibuprofen in patients with compromised renal haemodynamics. Br J Clin Pharmacol. 1995; 40: 67–2.PubMedCrossRefGoogle Scholar
  210. 210.
    Knights KM, McLean CF, Tonkin AL, et al. Lack of effect of gender and oral contraceptive steroids on the pharmacokinetics of (R)-ibuprofen in humans. Br J Clin Pharmacol. 1995; 40: 153–6.PubMedCrossRefGoogle Scholar
  211. 211.
    Cooper SA, Cowan A, Tallarida RJ, et al. The analgesic interaction of misoprostol with nonsteroidal anti-inflammatory drugs. Am J Ther. 1996; 3: 261–7.PubMedCrossRefGoogle Scholar
  212. 212.
    Siemon D, de Vries JX, Stozer F, et al. Fasting and postprandial disposition of R(−) and S(+)-ibuprofen. J Med Res. 1997; 2: 215–9.Google Scholar
  213. 213.
    Fornasini G, Monti N, Brogin G. Preliminary pharmacokinetic study of ibuprofen enantiomers after administration of a new oral formulation (ibuprofen arginine) to healthy male volunteers. Chirality. 1997; 9: 297–302.PubMedCrossRefGoogle Scholar
  214. 214.
    Hummel T, Cramer O, Mohammadian P, et al. Comparison of the antinociception produced by two oral formulations of ibuprofen: ibuprofeneffervescent vs ibuprofen tablets. Eur J Clin Pharmacol. 1997; 52: 107–14.PubMedCrossRefGoogle Scholar
  215. 215.
    Suri A, Grundy BL, Derendorf H. Pharmacokinetics and pharmacodynamics of enantiomers of ibuprofen and flurbiprofen after oral administration. In J Clin Pharmacol Ther. 1997; 35(1): 1–8.Google Scholar
  216. 216.
    Adams SS, Bough RG, Cliffe EE, et al. Some aspects of the pharmacology, metabolism and toxicology of ibuprofen. Rheumatol Phys Med 1970; Suppl. 9: 9–26.Google Scholar
  217. 217.
    Wagner JG, Albert KS, Szpunar GJ, et al. Pharmacokinetics of ibuprofen in man IV: absorption and disposition. J Pharmacokinet Biopharm. 1984; 12: 381–99.PubMedGoogle Scholar
  218. 218.
    Janssen GME, Venema JF. Ibuprofen: plasma concentrations in man. J Int Med Res. 1985; 13: 68–73.PubMedGoogle Scholar
  219. 219.
    Wagener HH, Vögtle-Junkert U. Intrasubject variability in bioequivalence studies illustrated by the example of ibuprofen. Int J Clin Pharm Ther. 1996; 34: 21–31.Google Scholar
  220. 220.
    Geisslinger G, Dietzel K, Bezler H, et al. Therapeutically relevant differences in the pharmackinetical and pharmaceutical behavior of ibuprofen lysinate as compared to ibuprofen acid. Int J Clin Pharmacol Ther Toxicol. 1989; 27: 324–8.PubMedGoogle Scholar
  221. 221.
    Adams SS, Warwick Buckler J. Ibuprofen and flurbiprofen. Clin Rheum Dis. 1979; 5: 359–78.Google Scholar
  222. 222.
    Averginos A, Noormohammadi A, Hutt AJ. Disposition of ibuprofen enantiomers following the oral administration of a novel controlled release formulation to healthy volunteers. Int J Pharm. 1991; 68: 97–103.CrossRefGoogle Scholar
  223. 223.
    Zhao GL, Wang HC. Drug release kinetics of ibuprofen coated granules and their in vitro in vivo correlation. Acta Pharm Sin. 1995; 30: 291–7.Google Scholar
  224. 224.
    Paliwal JK, Smith DE, Cox SR, et al. Stereoselective, competitive, and nonlinear plasma protein binding of ibuprofen enantiomers as determined in vivo in healthy subjects. J Pharmacokinet Biopharm. 1993; 21: 145–61.PubMedGoogle Scholar
  225. 225.
    Dominikus M, Nicolakis M, Kotz R, et al. Comparison of tissue and plasma levels of ibuprofen after oral and topical administration. Arzneimittel Forschung. 1996; 46(2): 1138–43.Google Scholar
  226. 226.
    Mondino A, Zanalo G, Giacheeti C, et al. Humankinetische Untersuchungen mit ibuprofen. Med Welt. 1983; 34: 1052–4.PubMedGoogle Scholar
  227. 227.
    Kaiser DG, Vangiessen GJ, Reischer RJ, et al. Isomeric inversion of ibuprofen (R)-enantiomer in humans. J Pharm Sci. 1976; 2: 269–73.CrossRefGoogle Scholar
  228. 228.
    Wechter WJ, Loughead DG, Reischer RJ, et al. Enzymatic inversion at saturated carbon: nature and mechanism of the inversion of R(−)p-iso-butyl hydratropic acid. Biochem Biophys Res Commun. 1974; 61: 833–7.PubMedCrossRefGoogle Scholar
  229. 229.
    Cheng H, Rogers JD, Demetriades JL, et al. Pharmacokinetics and bioinversion of ibuprofen enantiomers in humans. Pharm Res. 1994; 11: 824–30.PubMedCrossRefGoogle Scholar
  230. 230.
    Cox SR. Effect of route of administration on the chiral inversion of R(−)-ibuprofen [abstract]. Clin Pharmacol Ther. 1988; 21: 146.Google Scholar
  231. 231.
    Mehvar R, Jamali F. Pharmacokinetic analysis of the enantiomeric inversion of chiral nonsteroidal antiinflammatory drags. Pharm Res. 1988; 5: 76–9.PubMedCrossRefGoogle Scholar
  232. 232.
    Romero AJ, Rackley RJ, Rhodes CT. An evaluation of ibuprofen bioinversion by simulation. Chirality. 1991; 3: 418–21.PubMedCrossRefGoogle Scholar
  233. 233.
    Rudy AC, Knight PM, Brater DC, et al. Enantioselective disposition of ibuprofen in elderly persons with and without renal impairment. J Pharmacol Exp Ther. 1995; 273: 88–93.PubMedGoogle Scholar
  234. 234.
    Sawchuk RJ, Rector TS. Drug kinetics in burn patients. Clin Pharmacokinet. 1980; 5: 548–56.PubMedCrossRefGoogle Scholar
  235. 235.
    Albert KS, Gernaat CM. Pharmacokinetics of ibuprofen. Am J Med. 1984; 23: 40–6.CrossRefGoogle Scholar
  236. 236.
    Whitlam JB, Brown KR. Ultrafiltration in serum protein binding determinations. J Pharm Sci. 1981; 70: 146–50.PubMedCrossRefGoogle Scholar
  237. 237.
    Whitlam JB, Crooks MJ, Brown KF, et al. Binding of non-steroidal anti-inflammatory agents to proteins. I: ibuprofen-serum albumin interaction. Biochem Pharmacol. 1979; 28: 675–8.Google Scholar
  238. 238.
    Wanwimolrak S, Birkett DJ, Brooks PM. Protein binding of some non-steroidal anti-inflammatory drugs in rheumatoid arthritis. Clin Pharmacokinet. 1982; 7: 85–92.CrossRefGoogle Scholar
  239. 239.
    Vowles DT, Marchant B. Protein binding of ibuprofen and its relationship to drag interactions. Br J Clin Pract Symp Suppl. 1980; 1: 13–9.Google Scholar
  240. 240.
    Kober A, Sjöholm I. The binding sites on human serum albumin for some nonsteroidal anti-inflammatory drugs. Mol Pharmacol. 1980; 18: 421–6.PubMedGoogle Scholar
  241. 241.
    Montero MT, Estelrich J, Vails O. Binding of non-steroidal anti-inflammatory drugs to human serum albumin. Int J Pharm. 1990; 62: 21–5.CrossRefGoogle Scholar
  242. 242.
    Honoré B, Brodersen R. Albumin binding of anti-inflammatory drags: utility of a site-oriented versus a stoichiometric analysis. Mol Pharmacol. 1983; 25: 137–50.Google Scholar
  243. 243.
    Lockwood GF, Albert KS, Szupunar GJ, et al. Pharmacokinetics of ibuprofen in man — III: plasma protein binding. J Pharm Biopharm. 1983; 11: 469–82.Google Scholar
  244. 244.
    Sudlow G, Birkett DJ, Wade DN. Further characterization of specific drug binding sites on human serum albumin. Mol Pharmacol. 1976; 12: 1052–61.PubMedGoogle Scholar
  245. 245.
    Noctor TAG, Pham CD, Kaliszan R, et al. Stereochemical aspects of benzodiazepine binding to human serum albumin — 1: enantioselective high performance liquid affinity chromaotgraphic examination of chiral and achiral binding interactions between 1,4-benzodiazepines and human serum albumin. J Pharm Exp Ther. 1992; 42: 506–11.Google Scholar
  246. 246.
    Hage DS, Noctor TAG, Wainer IW. Characterization of the protein binding of chiral drugs by high-performance affinity chromatography interactions of R- and S-ibuprofen with human serum albumin. J Chromatogr. 1995; 693: 23–32.CrossRefGoogle Scholar
  247. 247.
    Hansen T, Day R, Williams K, et al. The assay and in vitro binding of the enantiomers of ibuprofen. Clin Exp Pharmacol Physiol. 1985; 9: 82–3.Google Scholar
  248. 248.
    Evans AM, Nation RL, Sansom LN, et al. Stereoselective plasma protein binding of ibuprofen enantiomers. Eur J Clin Pharmacol. 1989; 36: 283–90.PubMedCrossRefGoogle Scholar
  249. 249.
    Cheravallath VK, Riley CM, Narayanan SR, et al. A quantitative circular dichroic investigation of the binding of the enantiomers of ibuprofen and diclofenac to human serum albumin. J Pharm Biomed Anal. 1997; 15: 1719–24.CrossRefGoogle Scholar
  250. 250.
    Cheravallath VK, Riley CM, Narayanan SR, et al. The effect of octanoic acid on the binding of the enantiomers of ibuprofen and diclofenac to human serum albumin: a Chromatographic implication. Pharm Res. 1996; 13: 173–8.CrossRefGoogle Scholar
  251. 251.
    Glass RC, Swannell AJ. Concentrations of ibuprofen in serum and synovial fluid from patients with arthritis. Br J Clin Pract Sym Suppl. 1978; 6: 453P–54P.Google Scholar
  252. 252.
    Whitlam JB, Brown KF, Crooks MJ, et al. Transsynovial distribution of ibuprofen in arthritic patients. Clin Pharmacol Ther. 1981; 29: 487–92.PubMedCrossRefGoogle Scholar
  253. 253.
    Rau R, Berner G, Wagener HH, et al. Konzentration von ibuprofen und eiwess-gehalt sowie pH-wert in kniegelenkserguss und plasma nach oraler gabe von ibuprofen bei arthritis-patienten. Arzneimittel Forschung. 1989; 39: 1166–8.PubMedGoogle Scholar
  254. 254.
    Seideman P, Lohrer F, Graham GG, et al. The stereoselective disposition of the enantiomers of ibuprofen in blood, blister and synovial fluid. Br J Clin Pharm. 1994; 38: 221–7.CrossRefGoogle Scholar
  255. 255.
    Fears S. Lipophilic xenobiotic conjugates: the pharmacological and toxicological consequences of the participation of drugs and other foreign compounds as substrates in lipid biosynthesis. Prog Lipid Res. 1985; 24: 177–95.PubMedCrossRefGoogle Scholar
  256. 256.
    Williams K, Day R, Knihinicki R, et al. The stereoselective uptake of ibuprofen into adipose tissue. Biochem Pharmacol. 1986; 35: 3403–5.PubMedCrossRefGoogle Scholar
  257. 257.
    McGeer Pl, Schulzer M, McGeer EG. Arthritis and anti-inflammatory agents as possible protective factors for Alzheimer’s disease: a review of 17 epidemiologic studies. Neurology. 1996; 47(2): 425–32.PubMedCrossRefGoogle Scholar
  258. 258.
    Peters H, Chlud K, Berner G et al. Zur perkutanen kinetik von ibuprofen. Akt Rheumatol. 1987; 12: 208–11.CrossRefGoogle Scholar
  259. 259.
    Chlud K, Berner G, Wagener HH. Ibuprofenkonzentrationen in subkutanem fettgewebe, gelenkkapsel und synovialflüssigkeit nach perkutaner anwendung. Therapiewoche. 1985; 35: 2872–6.Google Scholar
  260. 260.
    Menzel EJ, Kolarz G. Bindungsvermögen von ibuprofen an humanes gewebe. Arzneimittel Forschung. 1992; 42: 325–7.PubMedGoogle Scholar
  261. 261.
    Menzel EJ, Kolarz G. Bindungsvermogen von ibuprofen an kollagen und andere bindegewebskomponenten. Arzneimittel Forschung. 1990; 40: 481–3.PubMedGoogle Scholar
  262. 262.
    Steinmetz JC, Lee CY, Wu A-Y. Tissue levels of ibuprofen after fatal overdosage of ibuprofen and acetaminophen. Vet Hum Toxicol. 1987; 29: 381–3.PubMedGoogle Scholar
  263. 263.
    Hutt AJ, Caldwell J. The metabolic chiral inversion of 2-arylpropionic acids-a novel route with pharmacological consequences. J Pharm Pharmacol. 1983; 35: 693–704.PubMedCrossRefGoogle Scholar
  264. 264.
    Mayer JM. Stereoselective metabolism of anti-inflammatory 2-arylpropionates. Acta Pharm Nord. 1990; 2: 197–216.PubMedGoogle Scholar
  265. 265.
    Nakamura Y, Yamaguchi T, Takahashi S, et al. Optical isomerization mechanism of R(−)-hydratropic acid derivatives [abstract]. J Pharmacobiodyn. 1981; 4: S–1.Google Scholar
  266. 266.
    Knihiniicki RD, Day RO, Williams KM. Chiral inversion of 2-arylpropionic acid non-steroidal anti-inflammatory drags — I: in vitro studies of ibuprofen and flurbiprofen. Biochem Pharmacol. 1989; 38: 4389–95.CrossRefGoogle Scholar
  267. 267.
    Knihiniicki RD, Day RO, Williams KM. Chiral inversion of 2-arylpropionic acid non-steroidal anti-inflammatory drags — II: racemization and hydrolysis of (R)- and (S)-ibuprofen CoA thioesters. Biochem Pharmacol. 1991; 42: 1905–11.CrossRefGoogle Scholar
  268. 268.
    Brugger R, Aliá BG, Reichel C, et al. Isolation and characterization of rat liver microsomal R-ibuprofenoyl-CoA synthetase. Biochem Pharmacol. 1996; 52: 1007–13.PubMedCrossRefGoogle Scholar
  269. 269.
    Chen C-Y, Lu P-H, Chen C-S. Metablic inversion of stereoisomeric ibuprofen in man. J Formos Med Assoc. 1991; 90: 437–42.PubMedGoogle Scholar
  270. 270.
    Chen C-S, Shieh W-R, Lu P-H, et al. Metabolic stereoisomeric inversion of ibuprofen in mammals. Biochem Biophy Acta. 1991; 1078: 411–7.CrossRefGoogle Scholar
  271. 271.
    Tracy TS, Hall SD. Metabolic inversion of (R)-ibuprofen epimerization and hydrolysis of ibuprofenyl-coenzyme A. Drug Metab Disp. 1991; 20: 322–7.Google Scholar
  272. 272.
    Tracy TS, Wirthwein DP, Hall SD. Metabolic inversion of (R)-ibuprofen: formation of ibuprofenyl-coenzyme A. Drug Metab Disp. 1992; 21: 114–20.Google Scholar
  273. 273.
    Menzel S, Waibel R, Brune K, et al. Is the formation of R-ibuprofenyl-adenylate the first stereoslective step of chrial inversion? Biochem Pharmacol. 1994; 48(5): 1056–8.PubMedCrossRefGoogle Scholar
  274. 274.
    Rudy AC, Knight PM, Brater DC, et al. Stereoselective metabolism of ibuprofen in humans: administration of R-, S- and racemic ibuprofen. J Pharmacol Exp Ther. 1991; 259: 1133–9.PubMedGoogle Scholar
  275. 275.
    Leeman TD, Tanson C, Bonnabry C, et al. A major role for cytochrome P450tb (CYP2C) subfamily in the actions of non-steroidal anti-inflammatory drugs. Drugs Exp Clin Res. 1993; 19: 189–95.Google Scholar
  276. 276.
    Hamman MA, Thompson GA, Hall SD. Regioselective and stereoselective metabolism of ibuprofen by human cytochrome P450 2C. Biochem Pharmacol. 1997; 54: 33–41.PubMedCrossRefGoogle Scholar
  277. 277.
    Castillo M, Lam F, Dooley MA, et al. Disposition and covalent binding of ibuprofen and its acylglucuronide in the elderly. Clin Pharmacol Ther. 1995; 57: 636–44.PubMedCrossRefGoogle Scholar
  278. 278.
    Spraul M, Hofmann, Dvortsak P, et al. High-performance liquid chromatography coupled to high-field proton nuclear magnetic resonance spectroscopy: application to the urinary metabolites of ibuprofen. Anal Chem. 1993; 65: 327–30.PubMedCrossRefGoogle Scholar
  279. 279.
    Wilson ID, Nicholson JK. Solid-phase extraction chromatography and nuclear magnetic resonance spectrometry for the identification and isolation of drug metabolites in urine. Anal Chem 1987; 2830–22.Google Scholar
  280. 280.
    Spraul M, Hofmann M, Dvortsak P, et al. Liquid chromatography coupled with high-field proton NMR for profiling human urine for endogenous compunds and drug metabolites. J Pharm Biomed Anal. 1992; 10(8): 601–5.PubMedCrossRefGoogle Scholar
  281. 281.
    Keep DR, Sidelmann UG, Hansen SH. Isolation and characterization of major phase I and II metabolites of ibuprofen. Pharm Res. 1997; 14(5): 676–80.CrossRefGoogle Scholar
  282. 282.
    Tan SC, Baker JA, Stevens N, et al. Synthesis, Chromatographic resolution and chiroptical properties of carboxyibuprofen stereoisomers: major metabolites of ibuprofen in man. Chirality. 1997; 9: 75–87.PubMedCrossRefGoogle Scholar
  283. 283.
    El Mouelhi M, Ruelius HW, Fenselau C, et al. Species-dependent enantioselective glucuronidation of three 2-arylpropionic acids diclofenac, ibuprofen and benoxaprofen. Drug Metab Disp. 1987; 15: 767–72.Google Scholar
  284. 284.
    Pettersen JE, Ulsaker GA, Jellum E. Studies on the metabolism of 2,4′-isobutylphenylpropionic acid (ibuprofen) by gas chromatography and mass spectrometry. J Chromatogr. 1978; 145: 413–20.PubMedCrossRefGoogle Scholar
  285. 285.
    Shirley MA, Guan X, Kaiser DG, et al. Taurine conjugation of ibuprofen in humans and in rat liver in vitro: relationship to metabolic chiral inversion. J Pharm Exp Ther. 1994; 269: 1166–75.Google Scholar
  286. 286.
    Chen CS, Chen T, Shieh WR. Metabolic stereoisomeric inversion of 2-arylpropionic acids: on the mechanism of ibuprofen epimerization in rats. Biochim Biophys Acta. 1990; 1033(1): 1–6.PubMedCrossRefGoogle Scholar
  287. 287.
    Chen CS, Shieh WR, Lu PH. Metabolic stereoisomeric inversion of ibuprofen in mammals. Biochim Biophys Acta. 1991; 1078(3): 411–7.PubMedCrossRefGoogle Scholar
  288. 288.
    Schneider HT, Nuernberg B, Dietzel K, et al. Biliary elimination of non-steroidal anti-inflammatory drugs. Br J Clin Pharmacol. 1990; 29: 127–31.PubMedCrossRefGoogle Scholar
  289. 289.
    Rudy AC, Anliker KS, Hall SD. High-performance liquid Chromatographic determination of the stereochemical metabolites of ibuprofen. J Chromatogr. 1990; 528: 395–405.PubMedCrossRefGoogle Scholar
  290. 290.
    Committee on Drugs, American Academy of Pediatrics. Transfer of drugs and other chemicals into human milk. Pediatrics. 1989; 79: 223–8.Google Scholar
  291. 291.
    Weibert RT, Townsend RJ, Kaiser DG, et al. Lack of ibuprofen secretion into milk. Clin Pharm 1982; 457–8.Google Scholar
  292. 292.
    Townsend RJ, Benedetti TJ, Erickson SH, et al. Excretion of ibuprofen into breast milk. Am J Obstet Gynecol. 1984; 149: 184–6.PubMedGoogle Scholar
  293. 293.
    Walter K, Dilger C. Ibuprofen in human milk. Br J Pharmacol. 1997; 44(2): 211–2.Google Scholar
  294. 294.
    Kimura T, Shirota O, Ohtsu Y. Analysis of ibuprofen metabolites by semi-microcolumn liquid chromatography with ultraviolet absorption and pulsed amperometric detectors. J Pharm Biomed Anal. 1997; 15: 1521–6.PubMedCrossRefGoogle Scholar
  295. 295.
    Wechter WJ. Understanding the chiral pharmacology of nonsteroidal antiinflammatory drugs in the aryl propionic acid class. J Clin Pharmacol. 1996; 36 Suppl. 12: 1S–2S.PubMedGoogle Scholar
  296. 296.
    Evans AM. Pharmacodynamics and pharmacokinetics of the profens: enantioselectivity, clinical implications, and special reference to S(+)-ibuprofen. J Clin Pharmacol. 1996; 36 Suppl. 12: 7S–15S.PubMedGoogle Scholar
  297. 297.
    Reichel C, Bang H, Brune K, et al. 2-Arylpropionyl-CoA epimerase: partial peptide sequences and tissue localization. Biochem Pharmacol. 1995; 50: 1803–6.PubMedCrossRefGoogle Scholar
  298. 298.
    Meyer JM. Ibuprofen enantiomers and lipid metabolism. J Clin Pharmacol. 1996; 36 Suppl. 12: 27S–32S.Google Scholar
  299. 299.
    Ahn H-Y, Jamali F, Cox SR, et al. Stereospelective disposition of ibuprofen enantiomers in the isolated perfused rat kidney. Pharm Res. 1991; 8: 1520–4.PubMedCrossRefGoogle Scholar
  300. 300.
    Cox PGE, Moons WM, Russel FGM, et al. Renal handling and effects of S(+)-ibuprofen and R(−)-ibuprofen in the rat isolated perfused kidney. Br J Pharmacol. 1991; 103: 1542–6.PubMedCrossRefGoogle Scholar
  301. 301.
    Caldwell J, Hutt AJ, Fournel-Gigleux S. The metabolic chiral inversion and disposition enantioselectivity of the 2-arylpropionic acids and their biological consequences. Biochem Pharmacol. 1988; 37: 105–14.PubMedCrossRefGoogle Scholar
  302. 302.
    Knihiniicki RD, Day RO, Graham GG, et al. Stereoselective disposition of ibuprofen and flurbiprofen in rats. Chirality. 1990; 2: 134–40.CrossRefGoogle Scholar
  303. 303.
    Leising G, Resel R, Tash S, et al. Physical aspects of dexibuprofen and racemic ibuprofen. J Clin Pharmacol. 1996; 36 Suppl. 12: 3S–6S.PubMedGoogle Scholar
  304. 304.
    Dwivedi SK, Mitchell AG, Sattari S, et al. Ibuprofen racemate and enantiomers: phase diagram, solubility and thermodynamic studies. Int J Pharm. 1992; 87: 95–104.CrossRefGoogle Scholar
  305. 305.
    Klein G, Neff H, Kullich W, et al. S(+) versus racemic ibuprofen [letter]. Lancet. 1992; 339: 681.PubMedCrossRefGoogle Scholar
  306. 306.
    Chlud K. Evaluation of tolerance and efficacy of S(+)-ibuprofen (Seractil®) in daily practice: a post-marketing-surveillance study in 1400 patients. J Clin Pharmacol. 1995; 35: 921–4.Google Scholar
  307. 307.
    Stock KP, Geisslinger G, Loew D, et al. S-ibuprofen versus ibuprofen-racemate. Rheumatol Int. 1991; 11: 199–202.PubMedCrossRefGoogle Scholar
  308. 308.
    Cullen DJ, Hudson N, Atherton JC, et al. Gastric tolerability of S(+) ibuprofen compared to racemic ibuprofen [abstract]. Gastroenterology. 1995; 108: A78.Google Scholar
  309. 309.
    Neupert W, Brugger R, Euchenhofer C, et al. Effects of ibuprofen enantiomers and its coenzyme A thioester on human prostaglandin endoperoxide synthases. Br J Pharmacol. 1997; 122: 487–92.PubMedCrossRefGoogle Scholar
  310. 310.
    Freneaux E, Fromety B, Berson A, et al. Stereoselective and nonstereoselective effects of ibuprofen enantiomers on mitochondrial β-oxidation of fatty acids. J Pharm Exp Ther. 1990; 255: 529–35.Google Scholar
  311. 311.
    Zhao B, Geisslinger G, Hall I, et al. The effect of the enantiomers of ibuprofen and flurbiprofen on the β-oxidation of palmitate in the rat. Chirality. 1992; 4: 137–41.PubMedCrossRefGoogle Scholar
  312. 312.
    Reichel C, Brugger R, Bang H, et al. Molecular cloning and expression of a 2-arylpropionyl-coenzyme a epimerase: a key enzyme in the inversion metabolism of ibuprofen. Mol Pharmacol. 1997; 51: 576–82.PubMedGoogle Scholar
  313. 313.
    Konstan MW, Byard PJ, Hoppel CL, et al. Effect of high-dose ibuprofen in patients with cystic fibrosis. N Engl J Med. 1995; 332: 848–54.PubMedCrossRefGoogle Scholar
  314. 314.
    Laska EM, Sunshine A, Marrero I. The correlation between blood levels of ibuprofen and analgesic response. Clin Pharmacol Ther. 1986; 40(1): 1–7.PubMedCrossRefGoogle Scholar
  315. 315.
    Greenan DW, Aarons L, Siddiqui M, et al. Dose-response study with ibuprofen in rheumatoid arthritis: clinical and pharmacokinetic findings. Br J Clin Pharmacol. 1983; 15: 311–6.CrossRefGoogle Scholar
  316. 316.
    Grennan DM, Ferry DG, Ashworth ME, et al. The aspirinibuprofen interaction in rheumatoid arthritis. Br J Clin Pharmacol. 1979; 8: 497–503.PubMedCrossRefGoogle Scholar
  317. 317.
    Bradley JD, Rudy AC, Katz BP, et al. Correlation of serum concentrations of ibuprofen stereoisomers with clinical response in the treatment of hip and knee osteoarthritis. J Rheumatol. 1992; 19: 130–4.PubMedGoogle Scholar
  318. 318.
    Malek KW, Velagapudi RB, Harter JG, et al. Pharmacodynamics of ibuprofen (IB) antipyresis in children [abstract]. Clin Pharmacol Ther. 1990; 20: 232.Google Scholar
  319. 319.
    Garg V, Jusko WJ. Pharmacodynamic modeling of nonsteroidal anti-inflammatory drugs: antipyretic effect of ibuprofen. Clin Pharmacol Ther. 1994; 55: 87–8.PubMedCrossRefGoogle Scholar
  320. 320.
    Milsom I, Anderch B. Intra-uterine pressure and serum ibuprofen: observations after oral administration of 400 mg ibuprofen to a patient with primary dysmenorrhoea. Eur J Clin Pharmacol. 1985; 29: 443–6.PubMedCrossRefGoogle Scholar
  321. 321.
    Hall AH, Smolinske SC, Conrad FL, et al. Ibuprofen overdose: 126 cases. Ann Emerg Med. 1986; 15: 1308–13.PubMedCrossRefGoogle Scholar
  322. 322.
    McElwee NE, Veltri JC, Bradford DC, et al. A prospective, population-based study of acute ibuprofen overdose: complications are rare and routine serum levels are not warranted. Ann Emerg Med. 1990; 19: 657–62.PubMedCrossRefGoogle Scholar
  323. 323.
    Jenkinson ML, Fitzpatrick R, Streete PJ, et al. The relationship between plasma ibuprofen concentrations and toxicity in acute ibuprofen overdose. Human Toxicol. 1988; 7: 319–24.CrossRefGoogle Scholar
  324. 324.
    Whelton A, Stout RL, Spilman PS, et al. Renal effects of ibuprofen, piroxicam, and sulindac in patients with asymptomatic renal failure. A prospective, randomized, crossover comparison. Ann Intern Med. 1990; 112: 568–76.Google Scholar
  325. 325.
    Murray MD, Black PK, Kuzmik DD, et al. Acute and chronic effects of nonsteroidal antiinflammatory drugs on glomerular filtration rate in elderly patients. Am J Med Sci. 1995; 310: 188–91.PubMedCrossRefGoogle Scholar
  326. 326.
    Adamska-Dyniewska, Tkaczewski W, et al. Farmakokinetyka ibuprofenu u chorych z marskoscia watroby. Wiad Lek. 1982; 35: 609–13.PubMedGoogle Scholar
  327. 327.
    Cooper-Peel C, Brodersen R, Robertston A. Does ibuprofen affect bilirubin-albumin binding in newborn infant serum? Pharm Toxicol. 1996; 79(6): 297–9.CrossRefGoogle Scholar
  328. 328.
    Grennan DM, Aarons L. Salicylate-NSAID interactions. Ann Rheum Dis 1994; 43: 351–2.CrossRefGoogle Scholar
  329. 329.
    Conrad KA, Mayershohn M, Bliss M. Cimetidine does not alter ibuprofen kinetics after a single dose. Br J Clin Pharmacol. 1984; 18: 624–6.PubMedCrossRefGoogle Scholar
  330. 330.
    Small RE, Wood JH. Influence of racial differences on effects of ranitidine and cimetidine on ibuprofen pharmacokinetics. Clin Pharm. 1989; 8: 471–2.PubMedGoogle Scholar
  331. 331.
    Nicholson PA, Karim A, Smith M. Pharmacokinetics of misoprostol in the elderly, in patients with renal failure and when co-administered with NSAID or antipyrine, propanolol or diazepam. J Rheumatol 1990; 20 Suppl.: S33–7.Google Scholar
  332. 332.
    Skeith KJ, Russell AS, Jamali F, et al. Lack of significant interaction between low dose methotrexate and ibuprofen or flurbiprofen in patients with arthritis. J Rheumatol. 1990; 17: 1008–10.PubMedGoogle Scholar
  333. 333.
    Abdullah ME, El-Sayed YM. Design of crossover microcomputer program and application on drug bioequivalence data. Comput Methods Programs Biomed. 1995; 48: 237–9.PubMedCrossRefGoogle Scholar
  334. 334.
    Ragheb M, Ban TA, Buchanan D, et al. Interaction of indomethacin and ibuprofen with lithium in manic patients under a steady-state lithium level. J Clin Psychiatry. 1980; 41: 397–8.PubMedGoogle Scholar
  335. 335.
    Tracy TS, Krohn K, Jones DR, et al. The effects of a salicylate, ibuprofen, and diclofenac on the disposition of methotrexate in patients with rheumatoid arthritis. Eur J Clin Pharmacol. 1992; 42: 121–5.PubMedCrossRefGoogle Scholar
  336. 336.
    Quattrocchi FP, Robinson JD, Curry RW, et al. The effects of ibuprofen on serum digoxin concentrations. Drug Intell Clin Pharm. 1983; 17: 286–8.PubMedGoogle Scholar
  337. 337.
    Goncalves I. Influence of ibuprofen on haemostasis in patients on anticoagulant therapy. J Int Med Res. 1973; 1: 180–5.Google Scholar
  338. 338.
    Boekhout-Mussert MJ, Loeliger EA. Influence of ibuprofen on oral anti-coagulation with phenprocoumon. J Int Med Res. 1974; 2: 279–83.Google Scholar
  339. 339.
    Thilo D, Nyman D, Duckert F. A study of the effects of the anti-rheumatic drug ibuprofen (brufen®) on patients being treated with the oral anti-coagulant phenprocoumon (marcoumar®). J Int Med Res. 1974; 2: 276–8.Google Scholar
  340. 340.
    Duckett F. The absence of effect of antirheumatic drug ibuprofen and oral anticoagulation with phenprocoumon. Curr Med Res Op. 1975; 3: 556–7.CrossRefGoogle Scholar
  341. 341.
    Penner JA, Abbrecht PH. Lack of interaction between ibuprofen and warfarin. Curr Ther Res. 1975; 18: 862–71.PubMedGoogle Scholar
  342. 342.
    Slattery JT, Levy G. Effect of ibuprofen on protein binding of warfarin in human serum. J Pharm Sci. 1977; 66: 1060.PubMedCrossRefGoogle Scholar
  343. 343.
    Schulman S, Henriksson K. Interaction of ibuprofen and warfarin on primary haemostasis. Br J Rheumatol. 1989; 28: 46–9.PubMedCrossRefGoogle Scholar
  344. 344.
    Koopmans PP, Thien TH, Gribnau FWJ. The influence of ibuprofen, diclofenac and sulindac on the blood pressure lowering effect of hydrochlorothiazide. Eur J Clin Pharmacol. 1987; 31: 553–7.PubMedCrossRefGoogle Scholar
  345. 345.
    Gurwitz JH, Everitt DE, Monane M, et al. The impact of ibuprofen on the efficacy of antihypertensive treatment with hydrochlorothiazide in elderly patients. J Gerontol 1996; 51A: M74–M79.CrossRefGoogle Scholar
  346. 346.
    Radack KL, Deck CC. Ibuprofen interferes with the efficacy of antihypertensive drugs: a randomized, double-blind, placebocontrolled trial of ibuprofen compared with acetaminophen. Ann Intern Med. 1987; 107: 628–35.PubMedGoogle Scholar
  347. 347.
    Wright JT, McKenney JM, Lehaney AM, et al. The effect of high-dose short-term ibuprofen on antihypertensive control with hydrochlorothiazide. Clin Pharmacol Ther. 1989; 46: 440–4.PubMedCrossRefGoogle Scholar
  348. 348.
    Minuz P, Lechi A, Arosio E, et al. Antihypertensive activity of enalapril. Effect of ibuprofen and different salt intakes. J Clin Hypertens. 1987; 3: 645–53.Google Scholar
  349. 349.
    Davies JG, Rawlins DC, Busson M. Effect of ibuprofen on blood pressure control by propranolol and bendrofluazide. J Int Med Res. 1988; 16: 173–81.PubMedGoogle Scholar
  350. 350.
    Hooten WM, Pearlson G. Delirium caused by tacrine and ibuprofen interaction. Am J Psychiatry. 1996; 153: 842.PubMedGoogle Scholar
  351. 351.
    Sandyk R. Phenytoin toxcity induced by interaction with ibuprofen. S Afr Med J. 1982; 62: 592.PubMedGoogle Scholar
  352. 352.
    Bachman KA, Schwartz JI, Forney RB, et al. Inability of ibuprofen to alter single dose phenytoin disposition. Br J Clin Pharmacol. 1986; 21: 165–9.CrossRefGoogle Scholar
  353. 353.
    Lee P, Bell MA, Webb J, et al. A study on the effects of ibuprofen on the metabolism of antipyrine in man. Med J Aust. 1973; 2: 846–9.PubMedGoogle Scholar

Copyright information

© Adis International Limited 1998

Authors and Affiliations

  1. 1.Facility of Medicine, Department of Pharmacology and TherapeuticsUniversity of CalgaryCalgaryCanada

Personalised recommendations