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

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Abstract
The kinetics of naproxen [(+)-6-methoxy-.alpha.-methyl-2-naphthaleneacetic acid] was studied relative to its inhibition of PG[prostaglandin]F2.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. PGF2.alpha. was measured by radioimmunoassay in platelet-rich plasma (PRP). The subjects were 4 healthy adult men and 5 dysmenorrheic women. Peak concentrations of naproxen varied between 26 and 69 .mu.g/ml and half-lifes varied between 9.5 and 21.9 h, .hivin.x [mean] = 16.4 h .+-. 4.4 (SD). Naproxen plasma protein binding exceeded 99.9%. The concentration of the metabolite was < 1% of naproxen and followed the same plasma concentration profile as the parent compound. The basal concentration of PGF2.alpha. varied between 0.13 and 6.3 ng/ml, .hivin.x = 1.5 .+-. 1.9 ng/ml. There was a marked decrease in the PGF2.alpha. concentration in thrombin-stimulated PRP during therapy and concentration was inversely correlated to the total plasma naproxen concentration.