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British Journal of Clinical Pharmacology logoLink to British Journal of Clinical Pharmacology
. 1994 May;37(5):453–456. doi: 10.1111/j.1365-2125.1994.tb05713.x

Methotrexate disposition following concomitant administration of ketoprofen, piroxicam and flurbiprofen in patients with rheumatoid arthritis.

T S Tracy 1, T Worster 1, J D Bradley 1, P K Greene 1, D C Brater 1
PMCID: PMC1364901  PMID: 8054251

Abstract

The effects of three non-steroidal anti-inflammatory drugs (NSAIDs) on the pharmacokinetics of methotrexate were studied in 10 patients with rheumatoid arthritis. Ketoprofen (3 mg kg-1 day-1), flurbiprofen (3 mg kg-1 day-1), piroxicam (20 mg day-1), or a non-NSAID control (paracetamol/acetaminophen) were administered to patients for at least 6 days (13 days in the case of piroxicam to establish steady state) in a randomized crossover design prior to receiving a weekly oral dose of methotrexate. In the non-NSAID control portion of the study, MTX oral clearance (CLo) was 11.0 +/- 3.9 l h-1, renal clearance (CLR) was 7.9 +/- 2.8 l h-1, percent excreted unchanged was 72 +2- 19% and fraction unbound (fu) was 0.54 +/- 0.11. Values of oral clearance, renal clearance, fraction unbound and percentage excreted unchanged of methotrexate varied no more than 12.2% from non-NSAID control during concomitant administration of ketoprofen, flurbiprofen or piroxicam and were not statistically different from non-NSAID control. In contrast to other NSAIDs such as ibuprofen and salicylates, ketoprofen, flurbiprofen or piroxicam in clinically relevant doses do not appear to affect methotrexate disposition and may be used safely in combination with methotrexate.

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Selected References

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  1. Albert K. S., Gernaat C. M. Pharmacokinetics of ibuprofen. Am J Med. 1984 Jul 13;77(1A):40–46. doi: 10.1016/s0002-9343(84)80017-0. [DOI] [PubMed] [Google Scholar]
  2. Arnett F. C., Edworthy S. M., Bloch D. A., McShane D. J., Fries J. F., Cooper N. S., Healey L. A., Kaplan S. R., Liang M. H., Luthra H. S. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum. 1988 Mar;31(3):315–324. doi: 10.1002/art.1780310302. [DOI] [PubMed] [Google Scholar]
  3. Chiou W. L. Critical evaluation of the potential error in pharmacokinetic studies of using the linear trapezoidal rule method for the calculation of the area under the plasma level--time curve. J Pharmacokinet Biopharm. 1978 Dec;6(6):539–546. doi: 10.1007/BF01062108. [DOI] [PubMed] [Google Scholar]
  4. Furst D. E., Herman R. A., Koehnke R., Ericksen N., Hash L., Riggs C. E., Porras A., Veng-Pedersen P. Effect of aspirin and sulindac on methotrexate clearance. J Pharm Sci. 1990 Sep;79(9):782–786. doi: 10.1002/jps.2600790907. [DOI] [PubMed] [Google Scholar]
  5. Ishizaki T., Sasaki T., Suganuma T., Horai Y., Chiba K., Watanabe M., Asuke W., Hoshi H. Pharmacokinetics of ketoprofen following single oral, intramuscular and rectal doses and after repeated oral administration. Eur J Clin Pharmacol. 1980 Nov;18(5):407–414. doi: 10.1007/BF00636794. [DOI] [PubMed] [Google Scholar]
  6. Koch P. A., Schultz C. A., Wills R. J., Hallquist S. L., Welling P. G. Influence of food and fluid ingestion on aspirin bioavailability. J Pharm Sci. 1978 Nov;67(11):1533–1535. doi: 10.1002/jps.2600671110. [DOI] [PubMed] [Google Scholar]
  7. Levy G., Tsuchiya T., Amsel L. P. Limited capacity for salicyl phenolic glucuronide formation and its effect on the kinetics of salicylate elimination in man. Clin Pharmacol Ther. 1972 Mar-Apr;13(2):258–268. doi: 10.1002/cpt1972132258. [DOI] [PubMed] [Google Scholar]
  8. Liegler D. G., Henderson E. S., Hahn M. A., Oliverio V. T. The effect of organic acids on renal clearance of methotrexate in man. Clin Pharmacol Ther. 1969 Nov-Dec;10(6):849–857. doi: 10.1002/cpt1969106849. [DOI] [PubMed] [Google Scholar]
  9. Nierenberg D. W. Competitive inhibition of methotrexate accumulation in rabbit kidney slices by nonsteroidal anti-inflammatory drugs. J Pharmacol Exp Ther. 1983 Jul;226(1):1–6. [PubMed] [Google Scholar]
  10. Richardson C. J., Blocka K. L., Ross S. G., Verbeeck R. K. Piroxicam and 5'-hydroxypiroxicam kinetics following multiple dose administration of piroxicam. Eur J Clin Pharmacol. 1987;32(1):89–91. doi: 10.1007/BF00609964. [DOI] [PubMed] [Google Scholar]
  11. Risdall P. C., Adams S. S., Crampton E. L., Marchant B. The disposition and metabolism of flurbiprofen in several species including man. Xenobiotica. 1978 Nov;8(11):691–703. doi: 10.3109/00498257809069581. [DOI] [PubMed] [Google Scholar]
  12. Rudy A. C., Knight P. M., Brater D. C., Hall S. D. Stereoselective metabolism of ibuprofen in humans: administration of R-, S- and racemic ibuprofen. J Pharmacol Exp Ther. 1991 Dec;259(3):1133–1139. [PubMed] [Google Scholar]
  13. Runkel R., Forchielli E., Boost G., Chaplin M., Hill R., Sevelius H., Thompson G., Segre E. Naproxen-metabolism, excretion and comparative pharmacokinetics. Scand J Rheumatol Suppl. 1973;2:24–36. [PubMed] [Google Scholar]
  14. Skeith K. J., Russell A. S., Jamali F., Coates J., Friedman H. Lack of significant interaction between low dose methotrexate and ibuprofen or flurbiprofen in patients with arthritis. J Rheumatol. 1990 Aug;17(8):1008–1010. [PubMed] [Google Scholar]
  15. Stewart C. F., Fleming R. A., Arkin C. R., Evans W. E. Coadministration of naproxen and low-dose methotrexate in patients with rheumatoid arthritis. Clin Pharmacol Ther. 1990 Apr;47(4):540–546. doi: 10.1038/clpt.1990.69. [DOI] [PubMed] [Google Scholar]
  16. Stewart C. F., Fleming R. A., Germain B. F., Seleznick M. J., Evans W. E. Aspirin alters methotrexate disposition in rheumatoid arthritis patients. Arthritis Rheum. 1991 Dec;34(12):1514–1520. doi: 10.1002/art.1780341207. [DOI] [PubMed] [Google Scholar]
  17. Thyss A., Milano G., Kubar J., Namer M., Schneider M. Clinical and pharmacokinetic evidence of a life-threatening interaction between methotrexate and ketoprofen. Lancet. 1986 Feb 1;1(8475):256–258. doi: 10.1016/s0140-6736(86)90786-5. [DOI] [PubMed] [Google Scholar]
  18. Tracy T. S., Krohn K., Jones D. R., Bradley J. D., Hall S. D., Brater D. C. The effects of a salicylate, ibuprofen, and naproxen on the disposition of methotrexate in patients with rheumatoid arthritis. Eur J Clin Pharmacol. 1992;42(2):121–125. doi: 10.1007/BF00278469. [DOI] [PubMed] [Google Scholar]

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