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

作者：Lisa J. Roberts, Brian J. Sweetman, J A Oates · 发表于：Journal of Biological Chemistry · 年份：1981 · DOI：10.1016/s0021-9258(19)68855-1 · 被引用次数：247 · 研究领域：Inflammatory mediators and NSAID effects、Clinical practice guidelines implementation、Pharmacogenetics and Drug Metabolism

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 arterie...