S-ibuprofen effectively inhibits thromboxane B2 levels and platelet function in an experimental model of lipopolysaccharide-stimulated and non-stimulated whole blood.
OBJECTIVE
The present study aimed at testing the effect of S- and R-ibuprofen on thromboxane B(2) (TXB(2)), collagen-epinephrine closure time (CEPI-CT) and collagen-adenosine 5'-diphosphate closure time (CADP-CT) in lipopolysaccharide (LPS)-stimulated and non-stimulated human whole blood.


METHODS
Whole blood was incubated with S- or R-ibuprofen with and without prior stimulation with LPS. To verify ibuprofen's potential effects on TXB(2), varying ratios of concentrations of S- and R-ibuprofen ranging from 0 to 100% were used. TXB(2) levels were measured by ELISA. The effects of S- and R-ibuprofen enantiomers on platelet aggregability were tested utilizing a PFA-100 apparatus.


RESULTS
In non-stimulated and LPS-stimulated whole blood, S-ibuprofen markedly decreased TXB(2) levels at concentrations ranging from 10 to 200 microg/ml. R-ibuprofen showed its inhibiting effect at concentrations >100 microg/ml. In inflammatory and non-inflammatory conditions, CEPI-CT was prolonged at concentrations of 12.5 and 75 microg/ml for S-ibuprofen and at a concentration of 150 microg/ml of combined R- and S-ibuprofen. S-ibuprofen was significantly more effective than R-ibuprofen (p < 0.05). The combined use of S- and R-ibuprofen did not additively or synergistically prolong CEPI-CTs. CADP-CTs remained unaffected by both enantiomers.


CONCLUSIONS
S-ibuprofen was more effective than the R-ibuprofen enantiomer in inhibiting TXB(2) plasma levels and aggregability of thrombocytes in non-inflammatory and inflammatory conditions.
Department of Clinical Pharmacology, Division of Clinical Pharmacokinetics, Medical University of Vienna, Vienna, Austria.
Stefan
S
Kaehler
Claudia
C
Marsik
Birgit
B
Heinisch
Christiane
C
Thallinger
Robert
R
Sauermann
Lili
L
Kazemi-Shirazi
Oswald
O
Wagner
Christian
C
Joukhadar
D000328:Adult; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007052:Ibuprofen / Q000737:chemistry* / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000633:toxicity*; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects* / Q000502:physiology; D010979:Platelet Function Tests / Q000379:methods; D013237:Stereoisomerism; D013929:Thromboxane B2 / Q000037:antagonists & inhibitors* / Q000097:blood* / Q000378:metabolism; D014914:Whole Blood Coagulation Time / Q000379:methods
D008070:Lipopolysaccharides; D013929:Thromboxane B2; D007052:Ibuprofen