Benoxaprofen: plasma binding and binding interactions with some drugs and endogenous compounds.

The binding of benoxaprofen to human serum albumin (HSA) was investigated by equilibrium dialysis at pH 7.4 and 37 degrees C. As most acidic drugs, almost completely ionized at plasma pH, benoxaprofen was avidly bound to HSA (7.5 x 10(-6) M) with the following parameters: n1 = 3.3 and K1 = 325 x 10(3) M-1; n2 = 16.2 and K2 = 2.1 x 10(3) M-1 At normal HSA plasma concentration in humans benoxaprofen was more than 99.5% bound, either when a pure HSA solution or when a pooled serum was used. Such results were obtained within a wide range of benoxaprofen concentrations and benoxaprofen binding did not significantly differ whatever its concentration might be. The influence of liver failure on benoxaprofen serum binding was investigated in five patients whose bilirubinaemia was from 15 to 28 x 10(-6) M, and the results were compared to those of five normal volunteers. There was no difference between the two groups: 99.30 +/- 0.30% versus 99.62 +/- 0.30%. However, in four other patients whose bilirubinaemia was greater than 130 x 10(-6) M, the binding of benoxaprofen decreased to 98.0 +/- 1.6% (p] less than 0.05). Addition of FFA (palmitic acid, 2000 . 10(-6) M) to H SA (580 x 10(-6) M) involved a slight decrease in HSA binding of benoxaprofen: 99.8 +/- 0.1 versus 99.66 +/- 0.03%. Serum binding of benoxaprofen was not affected by therapeutic levels of tolbutamide, was slightly decreased from 99.7 to 9.2% by furosemide, to 99.4% by CPIB, and to 99.4% by salicylic acid. At the reverse, therapeutic plasma levels of benoxaprofen did not displace warfarin and acenocoumarol, but they displaced CPIB from 90.1 to 86.1%, glibenclamide from 95.2 to 94.2% and phenylbutazone 99.6 to 93.0%.