salicylates and flavone-acetic-acid

Both the capacity of healthy human, cancer patient, and mouse plasma proteins to bind flavone acetic acid (FAA) and the qualitative differences in the plasma protein-binding site were studied. The binding capacity of plasma proteins for FAA was saturated within the therapeutic range in both species. The binding of FAA to plasma protein was significantly greater in both healthy human and cancer patient plasma than in mouse plasma. Plasma from patients with cancer bound on the average less FAA than did healthy patient plasma. The concentration of albumin in the plasma varied between healthy humans, cancer patients, and mice, being 5.3 +/- 0.7, 4.7 +/- 0.8, and 3.9 +/- 0.3 g/100 ml, respectively. The protein binding of FAA was found to be dependent on the plasma albumin concentration, but albumin concentration alone was not adequate for the accurate prediction of the percentage of FAA protein bound. Scatchard plots indicated that healthy human plasma had a greater number of high-affinity binding sites than did mouse plasma. FAA binds at the indolebenzodiazepine binding area on albumin and can be displaced from this site by salicylic acid and clofibric acid, but only at supratherapeutic concentrations. Our results indicate that alterations in plasma albumin could contribute to a variable effect with FAA. Therefore, the influence of serum albumin concentration and the nonlinearity of FAA protein binding should be considered in assessment of the appropriateness of a dose schedule for FAA.

Topics: Animals; Binding Sites; Binding, Competitive; Blood Proteins; Clofibric Acid; Flavonoids; Humans; In Vitro Techniques; Mice; Neoplasms; Protein Binding; Salicylates; Salicylic Acid; Serum Albumin