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Relation of naproxen kinetics to effect on platelet prostaglandin release in men and dysmenorrheic women
Author(s) -
Tomson Göran,
Lunell NilsOlov,
Oliw Ernst,
Rane Anders
Publication year - 1981
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.1981.27
Subject(s) - naproxen , chemistry , metabolite , radioimmunoassay , prostaglandin , chromatography , plasma concentration , basal (medicine) , endocrinology , medicine , pharmacology , biochemistry , alternative medicine , pathology , insulin
The purpose of our investigation was to determine kinetics of naproxen [(+)‐6‐methoxy‐α‐methyl‐2‐naphthaleneacetic acid] relative to its inhibition of PGF 2α 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. PGF 2α 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, x̄ = 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 PGF 2α varied between 0.13 and 6.3 ng/ml, x̄ = 1.5 ± 1.9 nglml. With no exception, there was a marked decrease in the PGF 2α 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