Differences in the in vitro antiplatelet effect of dexibuprofen, ibuprofen, and flurbiprofen in human blood.
BACKGROUND
In this study, we compared the in vitro pharmacodynamic profile of dexibuprofen, ibuprofen, and flurbiprofen to identify possible differences in antiplatelet activity.


METHODS
In whole blood samples from healthy volunteers, we measured platelet aggregation induced by adenosine diphosphate, collagen and arachidonic acid, platelet thromboxane B(2) (TxB(2)), lipopolysaccharide-induced prostaglandin E(2), leukocyte 6-keto-prostaglandin F(1α) (PGF(1α)), and nitric oxide induced by both constitutive and inducible pathways before and after incubation with increasing concentrations of acetylsalicylic acid, dexibuprofen, ibuprofen, or flurbiprofen. The concentration that inhibited (IC(50)) or increased each variable by 50% was calculated.


RESULTS
All 3 drugs inhibited platelet aggregation in a dose-dependent manner, TxB(2), prostaglandin E(2), and 6-keto-PGF(1α), and increased calcium-induced nitric oxide production. Dexibuprofen showed greater antiplatelet potency than ibuprofen and flurbiprofen, and its profile was similar to that of aspirin. For example, IC(50) values for arachidonic acid-induced platelet aggregation were 0.85 ± 0.06 μM for dexibuprofen, 14.76 ± 1.22 μM for ibuprofen, 6.39 ± 0.51 μM for flurbiprofen, and 0.38 ± 0.03 μM for aspirin. All drugs inhibited both thromboxane and prostacyclin synthesis, but the IC(50) anti-TxB(2)/IC(50) anti-6-keto-PGF(1α) ratio was 0.21 ± 0.03 for dexibuprofen, 1.05 ± 0.08 for ibuprofen, 0.79 ± 0.11 for flurbiprofen, and 0.46 ± 0.06 for aspirin. All drugs increased calcium-dependent nitric oxide production.


CONCLUSIONS
The aryl propionic acid derivative dexibuprofen was the most potent antiplatelet drug, and its pharmacodynamic profile is similar to aspirin.
Laboratorio de Investigaciones Antitrombóticas e Isquemia Tisular, Department of Pharmacology and Therapeutics, School of Medicine, University of Málaga, Málaga, Spain.
J P
JP
De la Cruz
J J
JJ
Reyes
M I
MI
Ruiz-Moreno
J A
JA
Lopez-Villodres
N
N
Jebrouni
J A
JA
Gonzalez-Correa
D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D000328:Adult; D001241:Aspirin / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D015232:Dinoprostone / Q000097:blood; D004305:Dose-Response Relationship, Drug; D005260:Female; D005480:Flurbiprofen / Q000494:pharmacology*; D006801:Humans; D007052:Ibuprofen / Q000031:analogs & derivatives* / Q000494:pharmacology; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009569:Nitric Oxide / Q000097:blood; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D013929:Thromboxane B2 / Q000097:blood
D010975:Platelet Aggregation Inhibitors; D009569:Nitric Oxide; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D005480:Flurbiprofen; C539402:dexibuprofen; D015232:Dinoprostone; D001241:Aspirin; D007052:Ibuprofen