Metabolism of thromboxane B2 in the cynomolgus monkey

Abstract

[5,6,8,9,11,12,14,15-3H8]-Thromboxane B2 was injected into the saphenous vein of female cynomolgus monkeys, and blood samples were withdrawn from the contralateral saphenous vein. The compound was eliminated from the circulation with a half-life of about 10 min after an initial rapid disappearance. Some more polar products appeared with time, and also small amounts of material less polar than thromboxane B2; however, the dominating compound in all blood samples was unconverted thromboxane B2. About 45% of the given dose of tritium was excreted into urine in 48 hrs. Several metabolites of thromboxane B2 were found. The major urinary metabolite was identified as dinorthromboxane B2 (about 32% of urinary radioactivity). Unconverted thromboxane B2 was also found in considerable amounts (13% of urinary radioactivity). It is concluded that 1) dehydrogenation at C-12 is not a major pathway in the degradation of this compound, in contrast to metabolism at the corresponding C-15 alcohol group of prostaglandins; 2) after having gained access to the circulation, thromboxane B2 is the main circulating compound; however, assay of thromboxane B2 in plasma will be complicated or precluded by large artifactual production of the compound by platelets during sample collection.