Equipotent inhibition by R(−)−, S(+)‐ and racemic ibuprofen of human polymorphonuclear cell function in vitro.

Abstract

1. The effects of racemic (rac) ibuprofen and its S(+)‐ and R(−)− enantiomers on functions of human polymorphonuclear cells (PMN) and platelets were studied in vitro. 2. Rac‐ibuprofen inhibited PMN functions (O2‐ generation, beta‐glucuronidase release, LTB4 formation). Similar IC50 values (40‐100 microM) were obtained for the S(+)‐ and R(‐ )‐enantiomers. 3. All forms of ibuprofen inhibited cyclooxygenase‐ related platelet functions (aggregation, thromboxane formation). The S(+)‐enantiomer was about twice as active as the racemate while the R(‐ )‐enantiomer was at least 10‐fold less active. This demonstrates that the S(+) is the only cyclooxygenase inhibitory component of the racemate. 4. The concentrations of rac‐ibuprofen in PMN and platelets were similar to those in the incubation medium and represented equal concentrations of the enantiomers. This indicates that neither interconversion nor tissue accumulation of the compounds occurred. 5. These data indicate that antineutrophil effects of ibuprofen on human PMN are independent of cyclooxygenase inhibition. Therefore, R(−)− ibuprofen may be superior to the S(+)‐isomer for the treatment of PMN‐ dependent inflammatory diseases. However, effective free drug concentrations may not be obtained in vivo.

Intestinal toxicity of ketoprofen-trometamol vs its enantiomers in rat. Role of oxidative stress

“…Therefore, significant increases of MPO activity caused by racemic (50 mg/kg) and R (-)-ketoprofen (25 mg/kg) treatments (Table 2) can not be attributed to S(+)-enatiomer initially present or produced from inversion. Although leukocyte accumulation is necessary but not sufficient to induce ulcer formation, our results confirm that the R (-)-enantiomers of arylpropionic acid derivatives can contribute to modifications in PMN functions [13,15,16] related with the fact that the combination of R (-)-and S(+)-enantiomers results in a significant increase in ulcer formation compared with that produced by the pure S(+)-enantiomer [13].…”

Stereoselective disposition of ibuprofen enantiomers in human cerebrospinal fluid.

“…It is usually considered that the pharmacodynamic properties of ibuprofen reside almost exclusively in the (S)-enantiomer [4]. The latter was reported to be about 160 times more potent than (R)-ibuprofen in inhibiting prostaglandin synthesis in vitro [4] but there are conflicting data [5].…”

Effect of the Enantiomers of Flurbiprofen, Ibuprofen, and Ketoprofen on Intestinal Permeability

“…4 It has also been suggested that (R)-ibuprofen may reduce renal function in isolated perfused rat kidney 5 and may cause changes in polymorphonuclear lymphocyte function. 6 The R enantiomer of etodolac, a non-2-arylpropionate NSAID which undergoes no chiral inversion, has been previously demonstrated to induce some degree of intestinal permeability changes in the rat. 7 Thus, the R enantiomers of these drugs may not be as inactive as once thought.…”