Flurbiprofen and Enantiomers in Ophthalmic Solution Tested as Inhibitors of Prostanoid Synthesis in Human Blood

Abstract

ABSTRACT

The purpose of this study was to assess the selectivity and potency of the nonsteroidal anti-inflammatory drag (NSAID), flurbiprofen, and its enantiomers in their inhibition of cyclooxygenase-1 (COX-1 ) and cyclooxygenase-2(COX-2). An assay was used with freshly drawn, heparinized human whole blood, incubated with 25 μM calcium ionophore A23187 during 60 min to produce thromboxane B₂ (TXB₂) by activity of COX-1 in platelets. Incubation with E. coli lipopolysaccharide (LPS) during 24 hr produced prostaglandin E₂ (PGE₂) by induction of COX-2 in monocytes, suppressing any possible contribution of COX-1 activity by the addition of acetylsalicylic acid. Concentration inhibition curves were determined with racemic, S(+), and R(-) flurbiprofen in final concentrations ranging from 10^-3 to 10^-10 M. The stereoselectivity of S(+) flurbiprofen vs. R(-) flurbiprofen, expressed as the reciprocal of the ratio of the concentrations giving 50% inhibition (IC₅₀), is 340 for COX-1 and 56 for COX-2. The selectivity for COX-1 vs. COX-2, expressed as the reciprocal ratio of the IC₅₀, was 32 for racemic, 16 for S(+), and 5.3 for R(-) flurbiprofen. Meloxicam in the same assay showed COX-2 selectivity with a ratio of 0.19.