Relationship between lipophilicity and binding to human serum albumin of arylpropionic acid non-steroidal anti-inflammatory drugs

A possible relationship between lipophilicity and binding to human serum albumin was investigated for 11 arylpropionate non-steroidal anti-inflammatory drugs. The lipophilic parameter was determined by a reversed-phase high-performance liquid chromatographic procedure :Is the capacity factor (k'). The binding of arylpropionic acids to human serum albumin was studied in vitro by equilibrium dialysis. For each compound, a Scatchard analysis was performed considering two classes of binding sites characterized by high-and low-affinity constants, K-1 and K-2, respectively. A linear relationship was found between lipophilicity and binding parameters, n(1)K(1) (r = 0.88, P < 0.0005) and n(2)K(2) (r=0.96, P<0.0002). These results suggest the role of hydrophobic interactions in the binding of arylpropionic acids to human serum albumin. (C) 1997 Elsevier Science B.V.