title: Flurbiprofen and enantiomers in ophthalmic solution tested as inhibitors of prostanoid synthesis in human blood.
abstract: The purpose of this study was to assess the selectivity and potency of the nonsteroidal anti-inflammatory drug (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 microM 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.
authors.affiliation: The Netherlands Ophthalmic Research Institute, Amsterdam. n.vanhaeringen@ioi.knaw.nl
authors.forename: N J
authors.initials: NJ
authors.lastname: van Haeringen
authors.forename: A A
authors.initials: AA
authors.lastname: van Sorge
authors.forename: J L
authors.initials: JL
authors.lastname: Van Delft
authors.forename: V M
authors.initials: VM
authors.lastname: Carballosa Coré-Bodelier
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects / Q000201:enzymology; D000001:Calcimycin / Q000494:pharmacology; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D015232:Dinoprostone / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D004926:Escherichia coli; D005480:Flurbiprofen / Q000494:pharmacology*; D006801:Humans; D007527:Isoenzymes / Q000097:blood*; D008070:Lipopolysaccharides / Q000494:pharmacology; D000077239:Meloxicam; D008565:Membrane Proteins; D009000:Monocytes / Q000187:drug effects / Q000201:enzymology; D009883:Ophthalmic Solutions / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000097:blood*; D013237:Stereoisomerism; D013843:Thiazines / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology; D013929:Thromboxane B2 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D009883:Ophthalmic Solutions; D013843:Thiazines; D013844:Thiazoles; D000001:Calcimycin; D013929:Thromboxane B2; D005480:Flurbiprofen; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone; D000077239:Meloxicam