Metabolism of thromboxane B2 in man. Identification of twenty urinary metabolites.

Abstract

SHs]Thromboxane Bz (12.2 Ci/mol) was infused into a healthy adult male.Urinary metabolites of thromboxane Bz were isolated by reversed phase partition chromatography and high performance liquid chromatography.Structural identification of metabolites was accomplished by gas chromatography-mass spectrometry.Twenty metabolites were identified.Three primary pathways of metabolism of thromboxane Bz were found.A small quantity of thromboxane Bz was excreted unchanged, representing 2.5% of total recovered radioactivity.Two additional metabolites retained the original thromboxane Bz hemiacetal ring; one of these metabolites, 2,3-dinor-thromboxane Bz, was the major urinary metabolite and represented 23.0% of total recovered radioactivity.The other, 2,3,4,5-tetranorthromboxane Bz, represented 5.3% of total recovered radioactivity.T w o metabolites representing 1.1% of total recovered radioactivity had initially undergone reduction of the hemiacetal ring and indicated a second but relatively minor pathway of metabolism.A major pathway of metabolism was found to involve dehydrogenation of the hemiacetal alcohol group of thromboxane Bz resulting in a series of metabolites with a 6lactone ring.Sixteen metabolites representing 29.3% of total recovered radioactivity were identified as products of this pathway of metabolism.Thromboxane Az is a labile metabolite of prostaglandin G2 with potent biological activity (1).TxA2' contracts vascular smooth muscle including that of the coronary arteries (2) and induces irreversible platelet aggregation (1).A means to assess production of thromboxanes in vivo in man should have important biological applications as a tool to investigate the role of thromboxanes in human disease.Since thromboxanes are released in substantial quantities from aggregating platelets, quantification of in vivo thromboxane production may provide a means to asses in vivo platelet aggregation and