Summary
The protein binding of 4 non-steroidal anti-inflammatory drugs and warfarin was investigated in 10 patients with rheumatoid arthritis and in a matched control group of patients with Osteoarthritis. There were no differences between the groups in the free fractions of the 5 drugs studied. Fluorescent probe studies also showed only minor differences between groups. The results do not support previous suggestions that drug protein binding is altered in rheumatoid arthritis. Albumin concentration was positively correlated with the binding of salicylate, but not with binding of the other 4 drugs. Fatty acid concentration was directly correlated with the binding of warfarin and indomethacin. Correlations between drugs with respect to protein binding were investigated, but only that between salicylate and ibuprofen was significant.
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Aylward, M. and Maddock, J.: Total and free plasma tryptophan concentrations in rheumatoid diseases. Journal of Pharmacy and Pharmacology 25: 570–572 (1973).
Birkett, D.J.; Myer, S.P. and Sudlow, G.: Effects of fatty acids on two specific drug binding sites on human serum albumin. Molecular Pharmacology 13: 987–992 (1977).
Birkett, D.J.; Myer, S.P. and Hagedorn, J.: Effect of fatty acids on the binding of drugs and bilirubin to human serum albumin, in Tillement (Ed) Advances in Pharmacology and Therapeutics, Vol. 7: Biochemical and Clinical Pharmacology, pp.125–134 (Pergamon Press, Oxford, New York 1978).
Denko, C.W.; Purser, D.B. and Johnson, R.M.: Amino acid composition of serum albumin in normal individuals and in patients with rheumatoid arthritis. Clinical Chemistry 16: 54–57 (1970).
Duncombe, W.G.: The colorimetric micro-determination of nonesterified fatty acids in plasma. Clinica Chimica Acta 9: 122–125 (1964).
Ekstrand, R.; Alvan, G. and Borgå, O.: Concentration dependent plasma protein binding of salicylate in rheumatoid patients. Clinical Pharmacokinetics 4: 137–143 (1979).
Kober, A. and Sjöholm, I.: The binding sites on human serum albumin for some nonsteroidal anti-inflammatory drugs. Molecular Pharmacology 18: 421–426 (1980).
McArthur, J.N.; Dawkins, P.D. and Smith, M.J.H.: The displacement of L-tryptophan and dipeptides from bovine aibumin in vitro and from human plasma in vivo by antirheumatic drugs. Journal of Pharmacy and Pharmacology 23: 393–398 (1971).
Nilsen, O.G.; Storstein, L. and Jacobsen, S.: Effect of heparin and fatty acids on the binding of quinidine and warfarin in plasma. Biochemical Pharmacology 26: 229–235 (1977).
Ropes, M.W.; Bennett, G.A.; Cobb, S.; Jacox, R. and Jessar, R.A.: Diagnostic criteria for rheumatoid arthritis, 1958 revision. Annals of Rheumatic Diseases 18: 49–53 (1959).
Selley, M.L.; Madsen, B.W. and Thomas, J.: Protein binding of tolmetin. Clinical Pharmacology and Therapeutics 24: 694–705 (1978).
Solomon, H.M.; Schrogie, J.J. and Williams, D.: The displacement of phenylbutazone-14C and warfarin-14C from human albumin by various drugs and fatty acids. Biochemical Pharmacology 17: 143–151 (1968).
Spector, A. and Santos, E.: Influence of free fatty acid concentration on drug binding to plasma albumin. Annals of the New York Academy of Sciences 226: 247–258 (1973).
Sudlow, G.; Birkett, D.J. and Wade, D.N.: Spectroscopic techniques in the study of protein binding: A fluorescence technique for the evaluation of the albumin binding and displacement of warfarin and warfarin-alcohol. Clinical and Experimental Pharmacology and Physiology 2: 129–140 (1975a).
Sudlow, G.; Birkett, D.J. and Wade, D.N.: The characterisation of two specific drug binding sites on human serum albumin. Molecular Pharmacology 11: 824–832 (1975b).
Yacobi, A. and Levy, G.: Intraindividual relationships between serum protein binding of drugs in normal subjects, patients with impaired renal function and rats. Journal of Pharmaceutical Sciences 66: 1285–1288 (1977).
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Wanwimolruk, S., Birkett, D.J. & Brooks, P.M. Protein Binding of some Non-steroidal Anti-inflammatory Drugs in Rheumatoid Arthritis. Clin Pharmacokinet 7, 85–92 (1982). https://doi.org/10.2165/00003088-198207010-00005
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DOI: https://doi.org/10.2165/00003088-198207010-00005