Molecular Pharmacology, Vol 18, 421-426, Copyright © 1980 by the American Society for Pharmacology and Experimental Therapeutics

The Binding Sites on Human Serum Albumin for Some Nonsteroidal Antiinflammatory Drugs

¹ Department of Pharmaceutical Biochemistry, Biomedical Center, University of Uppsala, Box 578, S-751 23 Uppsala, Sweden

The four antiinflammatory drugs azapropazone, flurbiprofen, ibuprofen, and naproxen all bind very strongly to serum albumin with association constants, K_a, of 5.0 x 10⁵, 5.0 x 10⁶, 1.3 x 10⁶, and 1.8 x 10⁶ M^-1, respectively. The binding constants were determined with albumin immobilized in microparticles and were shown to be in good agreement with those obtained with equilibrium dialysis. Ibuprofen, flurbiprofen, and naproxen are primarily bound to the diazepam site on the albumin molecule as shown in interaction studies with albumin immobilized in microparticles. This site is shared with, e.g., some antidiabetic agents and benzodiazepines. Azapropazone is primarily bound to the warfarin site, to which also other coumarin derivatives and, e.g., phenytoin and bilirubin are bound. The antiinflammatory drugs studied have small distribution volumes and low free fractions in plasma, which means that displacement from their binding sites may be of pharmacokinetic significance.

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ACKNOWLEDGMENT We thank Mrs. Elisabet Tidare for skillful technical assistance.