INTERACTIONS OF NONSTEROIDAL ANTIINFLAMMATORY DRUGS WITH PHOSPHOLIPIDS - COMPARISON BETWEEN OCTANOL BUFFER PARTITION-COEFFICIENTS AND CHROMATOGRAPHIC INDEXES ON IMMOBILIZED ARTIFICIAL MEMBRANES/

A set of seventeen nonsteroidal antiinflammatory drugs (NSAIDs), consi sting of structurally unrelated carboxylic acids and piroxicam, was ex amined by high-performance liquid chromatography (HPLC) on an immobili zed artificial membrane (IAM) column that is a solid-phase model of fl uid membranes. The chromatographic capacity factors extrapolated to 10 0% aqueous phase (log k(w)(IAM)) were compared with n-octanol/buffer l ipophilicity parameters. The interactions with phospholipids were much better predicted from the intrinsic partition coefficient, log P, tha n from the apparent partition value, log D-7.4, indicating that phosph olipids can counteract the influence of electrically charged functions of analytes on lipophilic interactions. The log k(w)(IAM) and log P v alues for both NSAIDs and structurally unrelated neutral compounds res ult in unique scale if uniquely partition-based mechanisms take place. However, an electrostatic repulsion component was observed for the NS AIDs bearing the carboxylic function directly linked to the aromatic r ing, and for ibuprofen. Hence, the IAM-derived scale is distinctive fr om the one obtained by lipophilic parameters. The IC50 values on cyclo oxygenase 2 (COX-2) in intact cells determined by different authors ha ve been successfully correlated with respective IAM parameters, wherea s no correlation was found with COX-1 activity data. These results sug gest that membrane affinity may represent an important prerequisite fo r the specific binding NSAIDs/COX-2.