S-ibuprofen effectively inhibits thromboxane B2 levels and platelet function in an experimental model of lipopolysaccharide-stimulated and non-stimulated whole blood

Pharmacology. 2008;81(2):181-6. doi: 10.1159/000111759. Epub 2007 Nov 28.

Abstract

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.

Materials and 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.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Ibuprofen / chemistry*
  • Ibuprofen / pharmacology*
  • Lipopolysaccharides / toxicity*
  • Male
  • Platelet Aggregation / drug effects*
  • Platelet Aggregation / physiology
  • Platelet Function Tests / methods
  • Stereoisomerism
  • Thromboxane B2 / antagonists & inhibitors*
  • Thromboxane B2 / blood*
  • Thromboxane B2 / metabolism
  • Whole Blood Coagulation Time / methods

Substances

  • Lipopolysaccharides
  • Thromboxane B2
  • Ibuprofen