Relation of naproxen kinetics to effect on platelet prostaglandin release in men and dysmenorrheic women

The purpose of our investigation was to determine kinetics of naproxen [(+)-6-methoxy-α-methyl-2-naphthaleneacetic acid] relative to its inhibition of PGF2α release during thromhin-induced platelet aggregation in man after a single oral dose of 250 or 500 mg. Naproxen and its metabolite 6-hydroxy-α-methyl-2-naphthaleneacetic acid were measured by high-performance, reversed-phase liquid chromatography with fiuorimetric detection. PGF2α was measured by radioimmunoassay in platelet-rich plasma (PRP). Our subjects were four healthy adult men and five dysmenorrheic women. Peak concentrations of naproxen varied between 26 and 69 µg/ml and half-lifes varied between 9.5 and 21.9 hr, x = 16.4 hr ± 4.4 (SD). Naproxen plasma protein binding exceeded 99.9%. The concentration of the metabolite was less than 1% of naproxen and followed the same plasma concentration profile as the parent compound. The basal concentration of PGF2α varied between 0.13 and 6.3 ng/ml, x = 1.5 ± 1.9 nglml. With no exception, there was a marked decrease in the PGF2α concentration in thrombin-stimulated PRP during therapy, and concentration was inversely correlated to the total plasma naproxen concentration. Clinical Pharmacology and Therapeutics (1981) 29, 168–173; doi:10.1038/clpt.1981.27