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- W2015013806 abstract "Thromboxane (TX) B2, the chemically stable hydration product of pro-aggregatory TXA2, undergoes two major pathways of metabolism in man, resulting in the formation of 2,3-dinor-TXB2 and 11-dehydro-TXB2, respectively. We have measured the excretion of the latter during the infusion of exogenous TXB2 over a 50-fold dose range in order to examine the fractional conversion of TXB2 to urinary 11-dehydro-TXB2 and to re-assess the rate of entry of endogenous TXB2 into the circulation. Four healthy male volunteers receeived 6-h intravenous infusions of the vehicle alone and TXB2 at 0.1, 1.0 and 5.0 ng · kg−1 · min−1 in random order. They were pretreated with aspirin 325 mg/d in order to suppress endogenous TXB2 production. Urinary 11-dehydro-TXB2 and 2,3-dinor-TXB2 were measured before, during and up to 24 h after the infusions and in aspirin-free periods, by means of NICI-GC/MS-validated radioimmunoassays. Aspirin treatment suppressed urinary 11-dehydro-TXB2 by 91%. The fractional elimination of 11-dehydro-TXB2 was independent of the rate of TXB2 infusion and averaged 6.8 ± 0.7%, as compared to 6.4 ± 0.9% for 2,3-dinor-TXB2. Interpolation of 11-dehydro-TXB2 values obtained in aspirin-free periods onto the linear relationship between the quantities of infused TXB2 and the amount of metabolite excreted in excess of control values (y = 0.0058x, r = 0.94, P < 0.001) permitted calculation of the mean rate of entry of endogenous TXB2 into the circulation as 0.12 ng · kg−1 · min−1. We conclude that: (a) urinary 11-dehydro-TXB2 is at least as abundant a conversion product of exogenously infused TXB2 as 2,3-dinor-TXB2; (b) its excretion increases linearly as a function of the rate of entry of TXB2 into the circulation up to approx. 40-fold the calculated rate of secretion of endogenous TXB2; (c) the latter is consistent with previous estimates based on monitoring of the β-oxidation pathway of TXB2 metabolism." @default.
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- W2015013806 date "1989-07-01" @default.
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- W2015013806 title "Fractional conversion of thromboxane B2 to urinary 11-dehydrothromboxane B2 in man" @default.
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- W2015013806 doi "https://doi.org/10.1016/0304-4165(89)90051-2" @default.
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