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Equipotent inhibition by R(-)-, S(+)- and racemic ibuprofen of human polymorphonuclear cell function in vitro
M Villanueva1, R Heckenberger, H Strobach
1Institut für Pharmakologie, Heinrich-Heine-Universität Düsseldorf, Federal Republic of Germany.
British Journal of Clinical Pharmacology
|March 1, 1993
Summary
R(-)-ibuprofen may be better for inflammatory diseases than S(+)-ibuprofen, as it impacts polymorphonuclear cells (PMN) differently. Racemic ibuprofen affects PMN functions independently of cyclooxygenase inhibition.
Area of Science:
- Pharmacology
- Immunology
- Inflammation Research
Background:
- Ibuprofen is a non-steroidal anti-inflammatory drug (NSAID) commonly used to treat pain and inflammation.
- It exists as a racemic mixture of S(+) and R(-) enantiomers, with the S(+) enantiomer primarily responsible for inhibiting cyclooxygenase (COX).
- The distinct roles of ibuprofen enantiomers on immune cells, particularly polymorphonuclear cells (PMN), are not fully elucidated.
Purpose of the Study:
- To investigate the in vitro effects of racemic (rac) ibuprofen and its S(+) and R(-) enantiomers on human polymorphonuclear cell (PMN) and platelet functions.
- To determine if the anti-PMN effects of ibuprofen are mediated through cyclooxygenase (COX) inhibition.
- To compare the efficacy of R(-) and S(+) enantiomers in modulating PMN and platelet activities.
Main Methods:
- In vitro study using human PMN and platelets.
- Assessed PMN functions including O2- generation, beta-glucuronidase release, and leukotriene B4 (LTB4) formation.
- Measured platelet aggregation and thromboxane formation.
- Determined IC50 values for racemic ibuprofen and its enantiomers on these functions.
- Analyzed drug concentrations in PMN and platelets to assess interconversion or accumulation.
Main Results:
- Racemic ibuprofen and both enantiomers inhibited PMN functions (O2- generation, beta-glucuronidase release, LTB4 formation) with similar IC50 values (40-100 microM).
- All forms of ibuprofen inhibited COX-related platelet functions; S(+) was twice as active as racemate, while R(-) was at least 10-fold less active, confirming S(+) as the COX inhibitory component.
- Drug concentrations in PMN and platelets mirrored incubation levels, indicating no interconversion or accumulation.
- PMN effects of ibuprofen were independent of COX inhibition.
Conclusions:
- The anti-PMN effects of ibuprofen are independent of cyclooxygenase inhibition.
- R(-)-ibuprofen may be more suitable for treating PMN-dependent inflammatory diseases due to its distinct effects on PMN.
- Further research is needed to determine if effective in vivo concentrations of R(-)-ibuprofen can be achieved.