Development of a GC-MS method for quantitation of 2, 3-dinor-TXB2 and determinations of the daily urinary excretion rates in healthy humans

Vesterqvist, O.; Gréen, Krister; Lincoln, F. H.; Sebek, Oldrich K.

doi:10.1016/0049-3848(84)90153-1

Cited by 49 publications

(14 citation statements)

References 9 publications

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“…In some instances, measurements of urinary metabolites have been made. 14,16,32 In the present study, we have shown that a single dose of 600 mg aspirin taken orally in normal volunteers will inhibit production of both of these compounds in vivo in response to a bleeding time injury, though 24 hours after the Heavey and coworkers27 gave volunteers an oral dose of 600 mg aspirin and then assessed bradykinin-stimulated PGI2 production at 30, 90, and 180 minutes and at 6 hours after aspirin. They found that production of prostacyclin had recovered by 6 hours.…”

Section: Influence Of Long-term Aspirin Therapymentioning

confidence: 53%

“…An additional five controls (age, [24][25][26][27][28][29][30][31][32][33][34][35] years) were studied after the initial trial had been completed. These subjects were placed on 2 weeks of single dose 325 mg aspirin/day and were studied before the start of aspirin therapy, 24 hours after the first aspirin dose, and 4 and 24 hours after the day-14 aspirin dose.…”

Section: Subjects and Methods Drugsmentioning

confidence: 99%

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In vivo measurement of thromboxane B2 and 6-keto-prostaglandin F1 alpha in humans in response to a standardized vascular injury and the influence of aspirin.

et al. 1989

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ing men produced more thromboxane B2 (3.99±0.76 ng/ml) than nonsmoking women (2.13±0.24 ng/ml). Female smokers produced more thromboxane B2 (5.01±0.97 ng/ml) than nonsmoking women. Twenty-four hours after a single dose of 600 mg aspirin, in vitro production of thromboxane B2 in response to collagen fell by 95%, whereas in vivo production of thromboxane B2 and 6-keto-PGF,a in bleeding time blood fell by 87% and 66%, respectively. Subjects with the lowest absolute levels of thromboxane B2 24 hours after aspirin were also those with the longest postaspirin bleeding times. Recovery of 6-keto-PGFla production was faster than recovery of thromboxane B2 production, but 6-keto-PGFI, production for most subjects was still below basal 72 hours after aspirin. The influence of two different doses of long-term aspirin (80 mg every other day and 325 mg daily) on the in vivo production of thromboxane B2 and 6-keto-PGFl. was studied in normals and diabetics. After 14 days of 80 mg aspirin every other day, thromboxane B2 and 6-keto-PGFIa production were both substantially inhibited (93% and 78%, respectively). After 14 days of 325 mg aspirin daily, thromboxane B2 production was similarly substantially inhibited (93%), whereas 6-keto-PGFIa was significantly less affected (only 45% inhibition). Study of a second group of five normal subjects confirmed that 6-keto-PGFl. production was significantly inhibited 24 hours after the first dose of 325 mg aspirin but was not significantly less than basal after 14 days of 325 mg aspirin. The results suggest that 325 mg aspirin daily is more antithrombotic compared with 80 mg every other day due to the superior preservation of prostacyclin production. (Circulation 1989;79:29-38) T hromboxane A2, a potent vasoconstrictor and platelet-aggregating agent produced by platelets, and prostacyclin, a potent vasodilator and platelet inhibitor produced by vascular tissue, are believed to exert critical modulatory roles in vivo.1,2 Variations in the production of these comFrom the

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Section: Influence Of Long-term Aspirin Therapymentioning

confidence: 53%

Section: Subjects and Methods Drugsmentioning

confidence: 99%

In vivo measurement of thromboxane B2 and 6-keto-prostaglandin F1 alpha in humans in response to a standardized vascular injury and the influence of aspirin.

et al. 1989

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“…The methods for quantitation of 2,3-dinor-TxB2 and 2,3-dinor-6-keto-PGF~, in urine have been described in detail previously [21,22]. Briefly, 400-500 ng of tetra-deuterated 2,3-dinor-6-keto-PGF1, and 400-500ng of tetra-deuterated 2,3-dinor-TxB2 were added to 10-20ml aliquots of the urine samples.…”

Section: Analytic Methodsmentioning

confidence: 99%

“…By using tetra-deuterated internal standards/carriers we have developed specific and accurate methods for quantitation of these urinary metabolites by gas chromatography-mass spectrometry (GC-MS) with multiple ion detection [21,22]. In previous studies we have determined the urinary excretion of 2,3-dinor-TxB2 and 2,3-dinor-6-keto-PGFl~ in healthy individuals under normal conditions and following drugs [6,[21][22][23][24].…”

Section: Introductionmentioning

confidence: 99%

“…In previous studies we have determined the urinary excretion of 2,3-dinor-TxB2 and 2,3-dinor-6-keto-PGFl~ in healthy individuals under normal conditions and following drugs [6,[21][22][23][24]. Those studies have shown that the excretion of both metabolites is relatively constant (_+ 20% SD) in one particular healthy individual and independent of urinary flow rate.…”

Section: Introductionmentioning

confidence: 99%

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Synthetic arterial grafts cause prolonged increase in the in vivo formation of thromboxane and prostacyclin in humans

et al. 1987

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To evaluate the in vivo production of thromboxane A2 and prostacyclin their major urinary metabolites were measured in patients following graft replacement of the abdominal aorta. Specific methods based on gas chromatography-mass spectrometry were used to measure the urinary excretion of 2,3-dinor-TxB2 and 2,3-dinor-6-keto-PGF1 alpha. The excretion of these metabolites increased tenfold and almost fortyfold during post-operative Day 1 and remained elevated 6-10 days p.o. In a group undergoing cholecystectomy smaller changes of shorter duration were seen. It is concluded from this study that synthetic grafts cause prolonged increase in the in vivo formation of thromboxane A2 and prostacyclin. The reason for the increased TxA2 formation is probably platelet interaction with the foreign surface, whereas the increase of PGI2 could be part of a vascular defense against induced thrombotic activity. Those increases may have pathophysiologic implications.

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Thromboxane Synthase Activity and Platelet Function After Furegrelate Administration in Man

Mohrland¹,

Lugt²,

Gorman³

et al. 1989

The Journal of Clinical Pharma

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Furegrelate sodium (U-63,557A), a pyridine-derivative thromboxane synthase inhibitor, was administered orally in single doses of 200 to 1600 mg to normal male subjects. Furegrelate produced a dose-related inhibition of thromboxane synthesis for 8-12 hours when measured either ex vivo from platelet-rich plasma (PRP) or in vivo from urine. In general, the extent of thromboxane synthesis inhibition was greater in PRP than in urine. Furegrelate significantly inhibited platelet aggregation, but the effect was variable and measurements of thromboxane synthase did not predict the impact on platelet aggregation. Bleeding times and coagulation parameters were not altered significantly. Furegrelate was well absorbed orally with Tmax = 1 hr and t1/2 = 3.5 to 5 hrs. There was no marked metabolism; elimination was primarily by renal excretion of parent compound. Thus, furegrelate is an effective inhibitor of thromboxane synthase in man with a relatively long biologic and circulating half-life.

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Development of a GC-MS method for quantitation of 2, 3-dinor-TXB2 and determinations of the daily urinary excretion rates in healthy humans

Cited by 49 publications

References 9 publications

In vivo measurement of thromboxane B2 and 6-keto-prostaglandin F1 alpha in humans in response to a standardized vascular injury and the influence of aspirin.

In vivo measurement of thromboxane B2 and 6-keto-prostaglandin F1 alpha in humans in response to a standardized vascular injury and the influence of aspirin.

Synthetic arterial grafts cause prolonged increase in the in vivo formation of thromboxane and prostacyclin in humans

Thromboxane Synthase Activity and Platelet Function After Furegrelate Administration in Man

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