Inhibition of thromboxane formation in vivo and ex vivo: implications for therapy with platelet inhibitory drugs.

摘要: The capacity of platelets to generate thromboxane A2, reflected by measurement serum B2 (TxB2), greatly exceeds the systemic production in vivo. Thus, it is possible that substantial but incomplete inhibition formation ex vivo would still allow marked augmentation To address this hypothesis, we administered aspirin 120 mg, a selective inhibitor synthase (TxSl), 3-(1H-imidazol-1-yl- methyl)-2-methyl-1H-indole-1-propanoic acid (UK-38, 485) 200 and combination both drugs 12 healthy volunteers measured effects on TxB2 urinary 2,3-dinor-thromboxane (Tx-M), an index endogenous biosynthesis. Although was maximally inhibited 94 +/- 1% after 96 2% TxSl, maximal depression Tx-M only 28 8% 37 9%, respectively. Combination with TxSl resulted small significant increase generation (98 v 1%; P less than 0.05), disproportionately greater fall synthesis (58 7%; 0.01). Consistent further platelet synthesis, addition abolished transient decline prostacyclin alone. Administration lower dose (20 mg) 6 subjects caused reduction (12 4%; 0.05) 48 2%. relationship between form (serum TxB2) (Tx-M) departed markedly from line identity. When total blockade approached, minor decrements result disproportionate actual These results imply pharmacologic must be virtually complete before thromboxane- dependent activation influenced