title: Relation between plasma concentration of indomethacin and its effect on prostaglandin synthesis and platelet aggregation in man.
abstract: The dose and plasma levels of indomethacin correlated with inhibition of prostaglandin synthesis as measured both by urinary excretion of the major metabolite of prostaglandin E2 (PGE-M) and by the release of prostaglandin E2 from thrombin-stimulated platelets. Considerable intersubject variability was observed in the suppression of PGE-M excretion. In some patients 37.5 mg indomethacin daily, usually considered subtherapeutic, caused suppression. Maximal suppression (greater than 90%) occurred in some after a daily dose of 75 mg, whereas 150 mg was required to achieve this level of inhibition in others. Suppression of the excretion of PGE-M by 60% occurred when the end of the dosage interval plasma levels of indomethacin were in the range 0.05 to 0.3 microgram/ml, which implies that a somewhat higher average steady-state concentration during the dosage interval was required to achieve this effect. A similar degree of inhibition of the release of PGE2 on thrombin-stimulated platelets was associated with the same range of plasma levels. Upon discontinuation of the drug, the levels of indomethacin in plasma decreased exponentially; inhibition of the release of PGE2 from platelets by indomethacin declined linearly with time and in parallel with the logarithm of the diminishing plasma levels.
mesh_terms: D000328:Adult; D001792:Blood Platelets / Q000378:metabolism; D001798:Blood Proteins / Q000378:metabolism; D006801:Humans; D007213:Indomethacin / Q000097:blood / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects*; D011458:Prostaglandins E / Q000096:biosynthesis*; D011485:Protein Binding
chemical_list: D001798:Blood Proteins; D011458:Prostaglandins E; D007213:Indomethacin