Effect of R and S enantiomers of naproxen on aggregation and thromboxane production in human platelets

The effects of R and S enantiomers of naproxen [(+)-6-methoxy-alpha-methyl- 2-naphthaleneacetic acid] were studied on platelet aggregation and on the production of thromboxane B2 from collagen-stimulated human platelets in order to determine the effect of each enantiomer in terms of cyclooxygenase inhibition. S-Naproxen caused inhibition of platelet aggregation in platelet-rich plasma and washed human platelets in a concentration-related fashion in the range 1-80 micrograms/L. A similar concentration-related suppression was noted for R-naproxen, but this inhibition was significantly less than that induced by S-naproxen for all concentrations except 1 micrograms/L. Similarly, both R- and S-naproxen (1-80 micrograms/L) caused a concentration-dependent suppression of thromboxane B2 production from platelet-rich plasma. These values were significant at all concentrations of drug (10-80 micrograms/L) except at 1 micrograms/L. Significant differences in thromboxane B2 production from washed human platelets were noted at concentrations of 10 and 25 micrograms/L. The findings support previous studies reported in the literature that S-naproxen is more active than R-naproxen. Our findings that S-naproxen is more active than R-naproxen on collagen-stimulated platelet aggregation and prostaglandin production suggest that the findings of greater activity of S isomer over the R isomer in animal models of inflammation may be a direct expression of the differential action on prostaglandin synthesis.