Kinetics of ibuprofen effect on platelet and endothelial prostanoid release.
Reciprocal control of platelet function in the circulation has been proposed for the platelet-produced platelet proaggregatory prostanoid thromboxane A2 (TxA2) and the vascular endothelium-produced antiaggregatory prostanoid prostacyclin (PGI2). Forty drug-free healthy subjects were given a single dose of ibuprofen (0, 8, 10, 12, or 14 mg/kg) in a randomized, double-blind study. Blood samples were drawn 0, 2, 4, and 6 hours and 7 days after dosing for determination in serum (from untreated or in vitro indomethacin-treated portions of the blood) of TxA2 and PGI2 by radioimmunoassay of their stable metabolites (TxB2 and 6-keto-PGF1 alpha). Maximal platelet release of TxA2 (untreated serum) was lower in all drug groups 2, 4, and 6 hours after dosing. There was no significant decrease in PGI2 release. All doses of ibuprofen (except 0 mg/kg) induced essentially identical plasma levels at the times of measurement (postpeak decline), and effects could not be distinguished by dose for 8, 10, 12, or 14 mg/kg at these times. It is concluded that ibuprofen induces antiplatelet effects for at least 6 hours while preserving normal antiplatelet mechanisms.
D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D000328:Adult; D001792:Blood Platelets / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D011464:Epoprostenol / Q000097:blood / Q000378:metabolism; D005260:Female; D006801:Humans; D007052:Ibuprofen / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D011863:Radioimmunoassay; D011897:Random Allocation; D013928:Thromboxane A2 / Q000097:blood; D013929:Thromboxane B2 / Q000097:blood; D013997:Time Factors
D013929:Thromboxane B2; D013928:Thromboxane A2; D015121:6-Ketoprostaglandin F1 alpha; D011464:Epoprostenol; D007052:Ibuprofen