Binding of tiaprofenic acid to human sera and isolated serum proteins

The serum protein binding of tiaprofenic acid (Surgam) has been investigated in vitro by equilibrium dialysis in a physiological buffer of pH 7.40 with a 14C-labelled tiaprofenic acid isotope. The stability of labelled and unlabelled tiaprofenic acid was good during dialysis and an irregular distribution of 6% impurities in the 14C-labelled tiaprofenic acid isotope preparation was corrected for. No differences were found between elderly (74 +/- 4 yrs) and young (32 +/- 6 yrs) individuals, both groups showing a serum protein binding of tiaprofenic acid of 99.0 +/- 0.15%. However, patients with impaired renal function (creatinine clearance 24 +/- 8 ml/min) showed a significantly lower binding of 98.5 +/- 0.35%. Albumin was identified as the main tiaprofenic acid binding protein in human serum with a high affinity binding site characterized by an in vitro dissociation constant, KD, of 3.8 x 10(-6) mol/l and a number of available binding sites, n, of 0.34. Tiaprofenic acid was found not to be displaced from serum protein binding sites by other highly bound drugs. It is concluded that tiaprofenic acid protein binding is characterized by small interindividual variations, but that the decreased binding of tiaprofenic acid in patients with renal failure should be paid some attention to.