INTERACTIONS OF NONSTEROIDAL ANTIINFLAMMATORY DRUGS WITH PHOSPHOLIPIDS - COMPARISON BETWEEN OCTANOL BUFFER PARTITION-COEFFICIENTS AND CHROMATOGRAPHIC INDEXES ON IMMOBILIZED ARTIFICIAL MEMBRANES/
F. Barbato et al., INTERACTIONS OF NONSTEROIDAL ANTIINFLAMMATORY DRUGS WITH PHOSPHOLIPIDS - COMPARISON BETWEEN OCTANOL BUFFER PARTITION-COEFFICIENTS AND CHROMATOGRAPHIC INDEXES ON IMMOBILIZED ARTIFICIAL MEMBRANES/, Journal of pharmaceutical sciences, 86(2), 1997, pp. 225-229
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.