Clinical Pharmacokinetics

, Volume 26, Issue 2, pp 107–120 | Cite as

Pharmacokinetics of Oxicam Nonsteroidal Anti-Inflammatory Agents

  • Klaus T. Olkkola
  • Aurora V. Brunetto
  • Mauri J. Mattila
Review Article Drug Disposition

Summary

Oxicam nonsteroidal anti-inflammatory drugs (NSAIDs) are a group of structurally closely related substances with anti-inflammatory, analgesic and antipyretic activities. They have a weakly acidic character and are extensively bound to plasma proteins.

Piroxicam, the most widely used oxicam, is well absorbed after oral administration. Peak plasma concentrations (Cmax) of the drug are reached within 2 to 4 hours. Piroxicam has a small volume of distribution and a low plasma clearance. It undergoes hepatic metabolism and only 5 to 10% is excreted unchanged in urine. The elimination half-life varies between 30 and 70 hours. Age of the patient and renal or hepatic dysfunction do not seem to have any major effect on the pharmacokinetics of piroxicam. The drug reduces the renal excretion of lithium to a clinically significant extent, but the clinical significance of piroxicam-aspirin (acetylsalicylic-acid) and piroxicam-acenocoumarol interaction has not been established. Ampiroxicam, droxicam and pivoxicam are prodrugs of piroxicam that have been synthesised to reduce piroxicam-related gastrointestinal irritation. All prodrugs are well absorbed, but Cmax values are reached later than those following administration of piroxicam.

Tenoxicam is used in the management of rheumatic and inflammatory diseases. Mean Cmax values are achieved 2 hours postdose. Food reduces the rate but not the extent of absorption. The oral bioavailability of tenoxicam is 100% and rectal bioavailability is 80%. Like piroxicam, tenoxicam has a low volume of distribution and low plasma clearance. It is eliminated through hepatic metabolism. The mean elimination half-life is 60 to 75 hours. The pharmacokinetics of tenoxicam are independent of patient age, or concurrent liver or renal diseases. High doses of aspirin have been shown to increase the elimination of tenoxicam, but this has little clinical significance.

Isoxicam was in widespread clinical use until its worldwide marketing was suspended because of fatal skin reactions. Isoxicam is completely absorbed, but Cmax values are not reached until 10 hours postdose. It has a low plasma clearance, approximately 5 ml/min (0.3 L/h), and low volume of distribution. The mean elimination half-life is 30 hours and does not appear to be affected by the age of the patient. Isoxicam potentiated the anticoagulant effect of warfarin, necessitating a 20% dosage reduction.

Lornoxicam differs from other oxicam NSAIDs because it has a short elimination half-life of 3 to 4 hours. On the basis of limited data, some individuals seem to eliminate lornoxicam very slowly, suggesting the presence of polymorphic metabolism.

The pharmacokinetics of cinnoxicam and sudoxicam have not been studied thoroughly. However, like other oxicams, they appear to be absorbed completely after oral administration. Although the development of sudoxicam was stopped because of frequent adverse effects, this drug is interesting because, unlike other oxicams, its appears to have nonlinear elimination pharmacokinetics.

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References

  1. Äärynen M, Palho M. Piroxicam capsules versus suppositories: a pharmacokinetic and clinical trial. Arzneimittel-Forschung 36: 744–747, 1986PubMedGoogle Scholar
  2. al-Ghamdi MS, al-Mohanna FA, al-Mustafa ZH, al-Saeed IS. The effect of haemodialysis on the pharmacokinetics of tenoxicam in patients with end-stage renal disease. European Journal of Clinical Pharmacology 43: 197–199, 1992PubMedCrossRefGoogle Scholar
  3. Ankier SI, Brimelow AE, Crome P, Johnston A, Warrington SJ, et al. Chlortenoxicam pharmacokinetics in young and elderly human volunteers. Postgraduate Medical Journal 64: 752–754, 1988PubMedCrossRefGoogle Scholar
  4. Bachman F. Correlation of plasma and synovial fluid concentrations of piroxicam in patients with rheumatoid arthritis. In Dessain (Ed.) Rheumatology in the eighties: an advance in therapy — piroxicam, pp. 41–44, Excerpta Medica, Princeton, 1981Google Scholar
  5. Bartlett A, Costa A, Martinez L, Roser R, Sagarra R, et al. The effect of antacid and ranitidine on droxicam pharmacokinetics. Journal of Clinical Pharmacology 32: 1115–1119, 1992PubMedGoogle Scholar
  6. Benveniste C, Striberni R, Dayer P. Indirect assessment of the enterohepatic recirculation of piroxicam and tenoxicam. European Journal of Clinical Pharmacology 38: 547–549, 1990PubMedCrossRefGoogle Scholar
  7. Berte F, Richelmi P. Clinical pharmacology of non-steroidal anti-inflammatory drugs: a new benzothiazine derivative — cinnoxicam. Minerva Medica 7: 811–830, 1988Google Scholar
  8. Bird HA, Allen JG, Dixon JS, Wright V. A pharmacokinetic comparison of tenoxicam in plasma and synovial fluid. British Journal of Rheumatology 24: 351–356, 1985aPubMedCrossRefGoogle Scholar
  9. Bird HA, Clarke AK, Fowler PD, Little S, Podgorski MR, et al. An assessment of tenoxicam, a nonsteroidal anti-inflammatory drug of long half life, in patients with impaired renal function suffering from osteoarthritis or rheumatoid arthritis. Clinical Rheumatology 4: 453–460, 1989CrossRefGoogle Scholar
  10. Bird HA, Francis RJ, Le Gallez P, Hill J, Dixon JS, et al. Single and multiple oral dose pharmacokinetics of tenoxicam in the elderly. European Journal of Rheumatology and Inflammation 8: 60–69, 1985cPubMedGoogle Scholar
  11. Bird HA, Hill J, Haw WM, Dixon JS, Harris PA, et al. A comparison of faecal blood loss caused by tenoxicam and piroxicam in normal healthy male volunteers. Current Medical Research and Opinion 9: 524–528, 1985bPubMedCrossRefGoogle Scholar
  12. Bollet AJ. Piroxicam serum levels in patients treated for rheumatoid diseases. Seminars in Arthritis and Rheumatism 14 (Suppl. 1): 25–28, 1985PubMedCrossRefGoogle Scholar
  13. Bontoux D, Phelip AGX, Fourtillan JB. Pharmacokinetics of piroxicam in synovial fluid, synovial membrane, and cartilage. In Richardson (Ed.) The rheumatological disease process: focus on piroxicam, Royal Society of Medicine International Congress and Symposium Series. No. 67, pp. 91–94, 1984Google Scholar
  14. Borondy PE, Michniewicz BM. Metabolic disposition of isoxicam in man, monkey, dog, and rat. Drug Metabolism and Disposition 12: 444–451, 1984PubMedGoogle Scholar
  15. Brooks PM, McCredie M, Prowse M, Podgorski M, Forrest M, et al. Pharmacokinetics and effects of isoxicam on renal function in patients with renal insufficiency. Pharmatherapeutica 4: 665–672, 1986PubMedGoogle Scholar
  16. Bury RW. Liquid Chromatographic assay of isoxicam in human plasma and urine. Journal of Chromatography 337: 156–159, 1985PubMedCrossRefGoogle Scholar
  17. Bury RW, Whitworth JA, Saines D, Kincaid-Smith P, Moulds RFW. Effect of impairment of renal function on the accumulation and disposition of isoxicam. European Journal of Clinical Pharmacology 28: 585–588, 1985PubMedCrossRefGoogle Scholar
  18. Caille G. Isoxicam: interactions with other drug regimens. In Amor (Ed.) Non-steroidal anti-inflammatory agents in the elderly, pp. 106–113, EULAR, Basel, 1984Google Scholar
  19. Campbell AJ, Ferry DG, Edwards IR. Pharmacokinetic projections for isoxicam and piroxicam in old and young subjects. British Journal of Rheumatology 24: 176–178, 1985PubMedCrossRefGoogle Scholar
  20. Crevoisier C, Gerber N, Ott H, Meyer J, Heizmann P. Simultaneous pharmacokinetics of tenoxicam in plasma and synovial fluid. Presented at the 1 st World Conference on Inflammation, Antirheumatics, Analgesics, Immunomodulators, Venice, 16–18 April, 1984Google Scholar
  21. Crevoisier C, Heizmann P, Forgo I, Dubach UC. Plasma tenoxicam concentrations after single and multiple oral doses. European Journal of Drug Metabolism and Pharmacokinetics 14: 23–27, 1989aPubMedCrossRefGoogle Scholar
  22. Crevoisier C, Zaugg PY, Heizmann P, Meyer J. Influence of liver cirrhosis upon the pharmacokinetics of tenoxicam. International Journal of Clinical Pharmacology Research 9: 327–334, 1989bPubMedGoogle Scholar
  23. Daftsios AC, Johnson EL, Keeley FJ, Gryczko C, Rawski V. High-performance liquid Chromatographic analysis of isoxicam in human plasma and urine. Journal of Chromatography 305: 145–151, 1984PubMedCrossRefGoogle Scholar
  24. Darragh A, Gordon AJ, O’Bryne H, Hobbs D, Casey E. Single dose and steady state pharmacokinetics of piroxicam in elderly vs. young adults. European Journal of Clinical Pharmacology 28: 305–309, 1985PubMedCrossRefGoogle Scholar
  25. Day RO, Lam S, Paull P, Wade D. Effect of food and various antacids on the absorption of tenoxicam. British Journal of Clinical Pharmacology 24: 323–328, 1987PubMedCrossRefGoogle Scholar
  26. Day RO, Pauli PD, Lam S, Swanson BR, Williams KM, et al. The effect of concurrent aspirin upon plasma concentrations of tenoxicam. British Journal of Clinical Pharmacology 26: 455–462, 1988PubMedCrossRefGoogle Scholar
  27. Day RO, Williams KM, Graham S, Handel M. The pharmacokinetics of total unbound concentrations of tenoxicam in synovial fluid and plasma. Arthritis and Rheumatism 34: 751–60, 1991PubMedCrossRefGoogle Scholar
  28. Dell D, Joly R, Meister W, Arnold W, Partos C, et al. The determination of tenoxicam and the isolation, identification and determination of RO 17-6661, its major metabolite, in human urine. Journal of Chromatography 317: 483–492, 1984PubMedCrossRefGoogle Scholar
  29. De Vere-Tyndall AG, Ansell BM, Piper S, Lyannage S. Piroxicam in synovial fluid. In Dessain (Ed.) Rheumatology in the eighties: an advance in therapy — piroxicam, pp. 45–51, Excerpta Medica, Princeton, 1981Google Scholar
  30. Dittrich P, Weite S, Magometschrigg D, Kukovetz WR, Mayerhofer S, et al. The effect of concomitantly administered antacids on the bioavailability of lornoxicam, a novel NSAID. Drugs under Experimental and Clinical Research 16: 57–62, 1990PubMedGoogle Scholar
  31. Dixon JS, Lacey LF, Pickup ME, Langley SJ, Page MC. A lack of pharmacokinetic interaction between ranitidine and piroxicam. European Journal of Clinical Pharmacology 39: 583–586, 1990PubMedCrossRefGoogle Scholar
  32. Dixon JS, Lowe JR, Galloway DB. Rapid method for the determination of either piroxicam or tenoxicam in plasma using high performance liquid chromatography. Journal of Chromatography 310: 455–459, 1984PubMedCrossRefGoogle Scholar
  33. Dupont D, Dayer P, Balant L, et al. Variations inter- et intraindividuelles du comportement du piroxicam. Pharmacocinétique chez l’homme en bonne santé et chez le malade en insuffisance rénale. Pharmaceutica Acta Helvetiae 57: 20–26, 1982PubMedGoogle Scholar
  34. Edwards IR, Ferry DG, Campbell AJ. Factors affecting the kinetics of two benzothiazine non-steroidal anti-inflammatory medicines, piroxicam and isoxicam. European Journal of Clinical Pharmacology 28: 689–692, 1985PubMedCrossRefGoogle Scholar
  35. Enz W, Jeunet F. Tenoxicam milk formulations in the treatment of rheumatic conditions. Scandinavian Journal of Rheumatology (Suppl. 80): 54–58, 1989Google Scholar
  36. Esquivel M, Cussenot F, Ogilvie RI, East DS, Shaw DH. Interaction of isoxicam with acetylsalicylic acid. British Journal of Clinical Pharmacology 18: 567–571, 1984PubMedCrossRefGoogle Scholar
  37. Esquivel M, Ogilvie RI, East DS, Shaw DH, Heathcote J. Pharmacokinetic disposition of isoxicam in hepatic cirrhosis. Clinical and Investigative Medicine 10: 363–367, 1987PubMedGoogle Scholar
  38. Esteve A, Martinez L, Roser R, Sagarra R. Pharmacokinetics of droxicam in rat and dog. Methods and Findings in Experimental Clinical Pharmacology 8: 423–429, 1986Google Scholar
  39. Esteve J, Faire AJ, Roser R. Pharmacological profile of droxicam. General Pharmacology 19: 49–54, 1988PubMedCrossRefGoogle Scholar
  40. Falkner FC, Twomey TM, Borgers AP, Garg D, Weidler D, et al. Disposition of ampiroxicam, a prodrug of piroxicam, in man. Xenobiotica 20: 645–52, 1990PubMedCrossRefGoogle Scholar
  41. Farnham DJ. Studies of isoxicam in combination with aspirin, warfarin sodium and cimetidine. Seminars in Arthritis and Rheumatism 12 (Suppl. 2): 179–183, 1982CrossRefGoogle Scholar
  42. Fenner H. Comparative biochemical pharmacology of the oxicams. Scandinavian Journal of Rheumatology (Suppl. 65): 97–101, 1987Google Scholar
  43. Ferry DG, Gazeley LR, Busby WJ, Beasley DMG, Edwards IR, et al. Enhanced elimination of piroxicam by administration of activated charcoal or cholestyramine. European Journal of Clinical Pharmacology 39: 599–601, 1990PubMedCrossRefGoogle Scholar
  44. Ferry N, Cuisinaud G, Ouzan D, Trepo C, Sassard J. Pharmacokinetics of isoxicam in hepatic disease. British Journal of Clinical Pharmacology 22: 143S–147S, 1986PubMedCrossRefGoogle Scholar
  45. Fléchet ML, Moore N, Chedeville JC, Paux G, Boismare F, et al. Fatal epidermal necrolysis associated with isoxicam. Lancet 2: 499, 1985PubMedCrossRefGoogle Scholar
  46. Francis RJ, Allen JG, Looi D, Dixon JS, Bird MA, et al. Pharmacokinetics of tenoxicam after oral administration in healthy human subjects of various single doses. European Journal of Drug Metabolism and Pharmacokinetics 12: 59–63, 1987PubMedCrossRefGoogle Scholar
  47. Francis RJ, Dixon JS, Lowe JR, Harris PS. The effects of food and of antacid on the single oral dose pharmacokinetics of tenoxicam. European Journal of Drug Metabolism and Pharmacokinetics 10: 309–314, 1985PubMedCrossRefGoogle Scholar
  48. George CF. Isoxicam: the evolving perspective. British Journal of Clinical Pharmacology 22 (Suppl. 2): 107S–189S, 1986Google Scholar
  49. George CF, Renwick AG, Darragh AS, Hosie J, Blake D, et al. A comparison of isoxicam pharmacokinetics in young and elderly subjects. British Journal of Clinical Pharmacology 22 (Suppl. 2): 129S–134S, 1986PubMedCrossRefGoogle Scholar
  50. Ghose K, Burch A. Measurement of renal function by double isotope techniques in elderly patients during tenoxicam therapy. Archives of Gerontology and Geriatrics 9: 115–122, 1989PubMedCrossRefGoogle Scholar
  51. Grace EM, Mewa AAM, Sweeney GD, Rosenfeld JM. Lowering of plasma isoxicam concentrations with acetylsalicylic acid. Journal of Rheumatology 13: 1119–1121, 1986PubMedGoogle Scholar
  52. Grace EM, Rosenfeld JM, Sweeney GD, Watson Buchanan W. The pharmacokinetics of isoxicam in elderly patients with rheumatoid arthritis. Current Medical Research and Opinion 10: 580–591, 1987PubMedCrossRefGoogle Scholar
  53. Guentert TW, Defoir R, Mosberg H. The influence of cholestyramine on the elimination of tenoxicam and piroxicam. European Journal of Clinical Pharmacology 34: 283–289, 1988PubMedCrossRefGoogle Scholar
  54. Guentert TW, Schmitt M, Defoir R. Acceleration of the elimination of tenoxicam by cholestyramine in the dog. Journal of Pharmacology and Experimental Therapeutics 238: 295–301, 1986PubMedGoogle Scholar
  55. Hartmann D, Kleinbloesem CH, Lucker PW, Vetter G. Study on the possible interaction between tenoxicam and furosemide. Arzneimittel-Forschung 37: 1072–1076, 1987PubMedGoogle Scholar
  56. Hartmann D, Korn A, Komjati M, Heinz G, Haefelfinger P, et al. Lack of effect of tenoxicam on dynamic responses to concurrent oral doses of glucose and glibenclamide. British Journal of Clinical Pharmacology 30: 245–252, 1990PubMedCrossRefGoogle Scholar
  57. Heintz RC, Ducarre JM, Blouin RA, Guenzi A. Influence of oral dose escalation on the pharmacokinetics of tenoxicam (Tilcotil) in healthy male subjects. Litera Rheumatologica 10: 9–15, 1988Google Scholar
  58. Heintz RC, Guentert TW. Pharmacokinetic profile of tenoxicam. In Fenner & Stoiber (Eds) Tenoxicam, a new nonsteroidal anti-inflammatory drug, Litera Rheumatologica Vol. 6, pp. 23–34, EULAR, Basel, 1986Google Scholar
  59. Heintz RC, Guentert TW, Crevoisier C, Jeunet F. Influence of age sex and disease on the pharmacokinetic of tenoxicam, a new nonsteroidal anti-inflammatory drug. Presented at the EULAR Symposium, Rome, 16–18 October, 1986Google Scholar
  60. Heintz RC, Guentert TW, Enrico JF, Dubach UC, Brandt R, et al. Pharmacokinetics of tenoxicam in healthy human volunteers. European Journal of Rheumatology and Inflammation 7: 33–44, 1984PubMedGoogle Scholar
  61. Hinderung PM, Hartmann D, Crevoisier C, Moser V, Heizmann P. Integrated plasma and synovial fluid pharmacokinetics of tenoxicam in patients with rheumatoid arthritis and osteoarthritis: factors determining the synovial fluid/plasma distribution ratio. Therapeutic Drug Monitoring 10: 250–260, 1988CrossRefGoogle Scholar
  62. Hitzenberg G, Radhofer-Welte S, Takacs F, Rosenow D. Pharmacokinetics of lornoxicam in man. Posgraduate Medical Journal 66 (Suppl. 4): S22–S27, 1990Google Scholar
  63. Hobbs DC. Pharmacokinetics of piroxicam in man. European Journal of Rheumatology and Inflammation 6: 40–45, 1983Google Scholar
  64. Hobbs DC, Twomey TM. Piroxicam pharmacokinetics in man: aspirin and antacid interaction studies. Journal of Clinical Pharmacology 19: 270–281, 1979PubMedGoogle Scholar
  65. Horber FF, Guentert TW, Weidekamm E, Heizmann P, Descoedres C, et al. Pharmacokinetics of tenoxicam in patients with impaired renal function. European Journal of Clinical Pharmacology 29: 697–701, 1986PubMedCrossRefGoogle Scholar
  66. Ishizaki T, Nomura T, Abe T. Pharmacokinetics of piroxicam, a new non-steroidal anti-inflammatory agent, under fasting and postprandial states in man. Journal of Pharmacokinetics and Bio-pharmaceutics 7: 369–381, 1979CrossRefGoogle Scholar
  67. Jacotot B. Interaction of piroxicam with oral anti-coagulants. In Piroxicam: a new non-steroidal anti-inflammatory agent. Proceedings of the IXth European Congress of Rheumatology, Academy Professional Information Services, New York, pp. 46–47, 1978Google Scholar
  68. Julkunen H, Michelson JE, Mattila MJ. Pain relief in relation to tissue piroxicam concentrations in hip osteoarthritis. Annals of Clinical Research 15: 99–103, 1983PubMedGoogle Scholar
  69. Kanazawa M, Ito H. The pharmacokinetics of 0.5% piroxicam gel in humans. European Journal of Rheumatology and Inflammation 8: 117, 1987Google Scholar
  70. Kerry RJ, Owen G, Michaelson S. Possible toxic interaction between lithium and piroxicam. Lancet 1: 418–419, 1983PubMedCrossRefGoogle Scholar
  71. Kinawi A, Siebler D. Zur Bindung von Oxicam-Derivativen an Humanserumalbumin. Arzneimittel-Forschung 38: 1089–1092, 1988PubMedGoogle Scholar
  72. Kinawi A, Teller C. Zur Bestimmung der Pharmaka-Albuminbindung in Puffer lösung mit Hilfe eines Modifizierten Ultrafiltrationverfahrens. Arzneimittel-Forschung 29: 1495, 1979PubMedGoogle Scholar
  73. Kobayashi S, Oba T, Oguchi K, Sakamoto K, Yasuhara H, et al. Pharmacokinetics of tenoxicam in healthy volunteers and geriatric patients. Rinsho Yakuri 15: 399–405, 1984CrossRefGoogle Scholar
  74. Kölle EU, Hengy H, Vollmer KO. Pharmacokinetics of isoxicam in man following oral administration. Arzneimittel-Forschung 33: 3–7, 1983aGoogle Scholar
  75. Kölle EU, Vollmer KO. Pharmacokinetics of isoxicam following intravenous, intramuscular, oral and rectal administration in healthy volunteers. British Journal of Clinical Pharmacology 22: 135S–141S, 1986PubMedCrossRefGoogle Scholar
  76. Kölle EU, Vollmer KO, Herrmann M. Pharmacokinetics of isoxicam following i.v. administration to rats, dogs, monkeys and humans. Naunyn-Schmiedeberg’s Archives of Pharmacology 324 (Suppl.): R69, 1983bGoogle Scholar
  77. Kurowski M, Dunky A. Transsynovial kinetics of piroxicam in patients with rheumatoid arthritis. European Journal of Clinical Pharmacology 34: 401–406, 1988PubMedCrossRefGoogle Scholar
  78. Laufen H, Leifold M, Reidel KD. The effect of activated charcoal on the gastrointestinal absorption and reabsorption of piroxicam in dog and man. In Aiache & Hirtx (Eds) Biopharmaceutics and pharmacokinetics, 2nd European Congress, Spain, April 24–27, 1984Google Scholar
  79. Lignière GC, Montagnini G, Alberici M, Acerbi D. Plasma and synovial fluid concentrations of piroxicam during prolonged treatment with piroxicam pivalic ester. Arzneimittel Forschung 37: 560–563, 1987Google Scholar
  80. Lingetti M, Bianchi A, Ciarimboli M, Policicchio D. Blood levels and onset of analgesic activity after short-term administration of piroxicam and ibuprofen, and effect of piroxicam on gastrin secretion. In Dessain (Ed.) Rheumatology in the eighties: an advance in therapy — piroxicam, pp. 35–40, Excerpta Medica, Amsterdam, 1980Google Scholar
  81. Mailhot C, Dahl SL, Ward JR. The effect of cimetidine on serum concentrations of piroxicam. Pharmacotherapy 6: 112–117, 1986PubMedGoogle Scholar
  82. Mäkelä AL, Olkkola KT, Mattila MJ. Steady state pharmacokinetics of piroxicam in children with rheumatic diseases. European Journal of Clinical Pharmacology 41: 79–81, 1991PubMedCrossRefGoogle Scholar
  83. Martinez L, Sanchez J, Roser R, Garcia-Barbal J, Sagarra R, Bartlett A. Single and multiple dose pharmacokinetics of a new NSAID (droxicam) in healthy volunteers. European Journal of Drug Metabolism and Pharmacokinetics 14: 303–307, 1989PubMedCrossRefGoogle Scholar
  84. Martinez L, Sanchez J. Pharmacokinetic profile of droxicam. European Journal of Rheumatology and Inflammation 11 (4): 10–14, 1991PubMedGoogle Scholar
  85. Martinez L, Sanchez J, Roser R, Garcia-Barbal J, Bartlett A, et al. Comparative study of the multiple dose pharmacokinetics and the tolerance of a new NSAID (droxicam) versus piroxicam in healthy volunteers. Methods and Findings in Experimental and Clinical Pharmacology 10: 729–737, 1988PubMedGoogle Scholar
  86. Nilsen OG, Walstad RA, Eckert AM, Heizmann P, Buckert A, et al. Single and multiple dose pharmacokinetics of tenoxicam in the elderly. European Journal of Clinical Pharmacology 35: 563–566, 1988PubMedCrossRefGoogle Scholar
  87. Nuotio P, Mäkisara P. Pharmacokinetic and clinical study of piroxicam. In O’Brien & Wiseman (Eds) Piroxicam, Royal Society of Medicine International Congress and Symposium Series, No. 1, pp. 25–30, London Academic Press, London, 1978Google Scholar
  88. Østensen M. Piroxicam in human breast milk. European Journal of Clinical Pharmacology 25: 829–830, 1983PubMedCrossRefGoogle Scholar
  89. Palacios G, Castell O, Colombo M, Roser R, Esteve J. Comparative light and electron microscopic observations of lesive effects of two non-steroid antiinflammatory drugs plus stress on rat gastric mucosa. Methods and Findings in Experimental and Clinical Pharmacology 9: 353–370, 1987PubMedGoogle Scholar
  90. Pickup MI, Lowe JR, Galloway DB. Determination of Ro 120068, a new anti-inflammatory and analgesic compound, in plasma by means of high-performance liquid chromatography. Journal of Chromatography 225: 493–497, 1981PubMedCrossRefGoogle Scholar
  91. Pruss TP, Stroissnig H, Radhofer-Weite S, Wendtlandt W, Mehdi N, et al. Overview of the pharmacological properties, pharmacokinetics and animal saftey assessment of lornoxicam. Postgraduate Medical Journal (Suppl. 4): S18–S21, 1990Google Scholar
  92. Rau R. Interaction study of piroxicam with digoxin. In Piroxicam: a new non-steroidal anti-inflammatory agent. Proceedings of the IXth European Congress of Rheumatology, pp. 41–46, Academy Professional Information Services, New York, 1978Google Scholar
  93. Ravic M, Johnston A, Takacs F, Rosenow DE. The effect of repeated oral doses of lornoxicam on antipyrine elimination in normal human volunteers. Human and Experimental Toxicology 10: 375–377, 1991PubMedCrossRefGoogle Scholar
  94. Ravic M, Johnston A, Turner P. Clinical pharmacological studies of some possible interactions of lornoxicam with other drugs. Postgraduate Medical Journal 66 (Suppl. 4): S30–S34, 1990aPubMedGoogle Scholar
  95. Ravic M, Johnston A, Turner P, Ferber HP. A study of the interaction between lornoxicam and warfarin in healthy volunteers. Human and Experimental Toxicology 9: 413–414, 1990bPubMedCrossRefGoogle Scholar
  96. Richardson CJ, Blocka LN, Ross SG, Verbeeck RK. Effects of age and sex on piroxicam disposition. Clinical Pharmacology and Therapeutics 37: 13–18, 1985PubMedCrossRefGoogle Scholar
  97. Richardson CJ, Ross SG, Blocka KL, Verbeeck RK. High performance liquid Chromatographic analysis of piroxicam and its major metabolite 5′hydroxypiroxicam in human plasma and urine. Journal of Chromatography 382: 382–388, 1986PubMedCrossRefGoogle Scholar
  98. Rogers HJ, Spector RG, Morrison PJ, Bradbrook ID. Comparative steady-state pharmacokinetic study of piroxicam and flurbiprofen in normal subjects. European Journal of Rheumatology and Inflammation 4: 303–304, 1981PubMedGoogle Scholar
  99. Rowland M, Tozer TN. Clinical pharmacokinetics: concepts and applications, 2nd ed., pp. 222–237, Lea & Febiger, Philadelphia, 1989Google Scholar
  100. Said SA, Foda AM. Influence of cimetidine on the pharmacokinetics of piroxicam in rat and man. Arzneimittel-Forschung 39: 790–792, 1989PubMedGoogle Scholar
  101. Schiantarelli P, Acerbi D, Bovis G. Some pharmacokinetic properties and bioavailability by oral and rectal route of piroxicam in rodents and in man. Arzneimittel-Forschung 31: 92–97, 1981PubMedGoogle Scholar
  102. Schoog M, Laufen H, Dessain P. A comparison of the pharmacokinetics of piroxicam with those of plain and slow release indomethacin: a crossover study. European Journal of Rheumatology and Inflamation 4: 298–302, 1981Google Scholar
  103. Tilstone WJ, Lawson DH, Omara F, Cunningham F. The steady-state pharmacokinetics of piroxicam: effect of food and iron. European Journal of Rheumatology and Inflammation 4: 309–313, 1981PubMedGoogle Scholar
  104. Turner P, Johnston A. Clinical pharmacokinetic studies with lornoxicam. Postgraduate Medical Journal 66 (Suppl. 4): S28–S29, 1990PubMedGoogle Scholar
  105. Twomey TM, Bartolucci SR, Hobbs DC. Analysis of piroxicam in plasma by high-performance liquid chromatography. Journal of Chromatography 183: 104–108, 1980PubMedCrossRefGoogle Scholar
  106. Twomey TM, Hobbs DC. Biotransformation of piroxicam by man. Federation Proceedings 37: 271–280, 1978Google Scholar
  107. Ungethüm W. Study on the interaction between sulcralfate and diclofenac/piroxicam in healthy volunteers. Arzneimittel-Forschung 41: 797–800, 1991PubMedGoogle Scholar
  108. Verbeeck RK, Richardson CJ, Blocka KLN. Age and piroxicam disposition in rheumatoid arthritis. Clinical Pharmacology and Therapeutics 39: 233, 1986Google Scholar
  109. Wiseman EH, Boyle JA. Piroxicam (feldene). Clinics in Rheumatic Diseases 6: 585–613, 1981Google Scholar
  110. Wiseman EH, Chiani J. Antiinflammatory and pharmacokinetic properties of sudoxicam N-(2-thiazolyl)-4-hydroxy-2-methyl-2H-1,2-benzothiazine-3-carboxamide 1,1-dioxide. Biochemical Pharmacology 21: 2323–2334, 1972PubMedCrossRefGoogle Scholar
  111. Woolf TF, Black A, Chang T. In vitro metabolism of isoxicam by horseradish peroxidase. Xenobiotica 19 (12): 1369–1377, 1989PubMedCrossRefGoogle Scholar
  112. Woolf TF, Radulovic LL. Oxicams: metabolic disposition in man and animals. Drug Metabolism Reviews 21: 255–276, 1989PubMedCrossRefGoogle Scholar
  113. Woolf AD, Rogers HJ, Bradbrook ID, Corless D. Pharmacokinetic observations on piroxicam in young adult, middle-aged and elderly patients. British Journal of Clinical Pharmacology 16: 433–437, 1983PubMedCrossRefGoogle Scholar
  114. Yakatan G. Pharmacology and pharmacokinetics of isoxicam. Seminars in Arthritis and Rheumatism 12 (Suppl. 2): 154–159, 1982CrossRefGoogle Scholar

Copyright information

© Adis International Limited 1994

Authors and Affiliations

  • Klaus T. Olkkola
    • 1
  • Aurora V. Brunetto
    • 1
  • Mauri J. Mattila
    • 1
  1. 1.Departments of Anaesthesia and Pharmacology and ToxicologyUniversity of HelsinkiHelsinkiFinland
  2. 2.Department of AnaesthesiaUniversity of HelsinkiHelsinkiFinland

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