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-alpha-methyl-2-naphthaleneacetic acid] relative to its inhibition of PGF 2 alpha release during thrombin-induced platelet aggregation in man after a single oral dose of 250 or 500 mg. Naproxen and its metabolite 6-hydroxy-alpha-methyl-2-naphthaleneacetic acid were measured by high-performance, reversed-phase liquid chromatography with fluorimetric detection. PGF 2 alpha 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 microgram/ml and half-lifes varied between 9.5 and 21.9 hr, mean = 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 based concentration of PGF 2 alpha varied between 0.13 and 6.3 ng/ml, mean = 1.5 +/- 1.9 ng/ml. With no exception, there was a marked decrease in the PGF 2 alpha concentration in thrombin-stimulated PRP during therapy, and concentration was inversely correlated to the total plasma naproxen concentration.