European Journal of Clinical Pharmacology

, Volume 45, Issue 3, pp 283–286 | Cite as

Changes in plasma and urinary 11-dehydrothromboxane B2 in healthy subjects produced by oral CS-518, a novel thromboxane synthase inhibitor

  • T. Uematsu
  • W. Takasaki
  • K. Kosuge
  • K. Wada
  • H. Matsuno
  • Y. Tanaka
  • N. Yamamura
  • M. Nakashima
Short Communications

Summary

When 50 mg CS-518, a novel thromboxane (TX) A2 synthase inhibitor, was orally administered to healthy male volunteers, the plasma concentration of CS-518 peaked after 0.5 h and then decreased with a half-life of 0.44 h. There was no significant change in the plasma concentration of circulating TXB2, whereas that of circulating 11-dehydrothromboxane B2 (11-dhTXB2), an enzymatic metabolite of TXB2, was significantly decreased from 0.5 h to 24 h after administration; the maximal decrease to about 25% of the pre-dose value was found at 6 h.

After CS-518 100 mg b.d. for 4.5 days, plasma 11-dhTXB2 was suppressed to the same extent as after the single dose of 50 mg from 6 h after the initial dose throughout the administration period. The urinary excretion of 11-dhTXB2 corrected for the creatinine level was significantly decreased by 70–84% throughout the treatment.

These results suggest that CS-518 causes long-lasting inhibition of TXA2 synthase despite its rapid elimination from plasma, and that circulating 11-dhTXB2 in plasma and its urinary excretion can serve as a quantitative index of TXA2 synthase inhibition in vivo by CS-518.

Key words

Thromboxane synthase inhibitor CS-518 11-dehydrothromboxane B2 enzyme immunoassay thromboxane B2 

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Copyright information

© Springer-Verlag 1993

Authors and Affiliations

  • T. Uematsu
    • 1
  • W. Takasaki
    • 2
  • K. Kosuge
    • 1
  • K. Wada
    • 1
  • H. Matsuno
    • 1
  • Y. Tanaka
    • 2
  • N. Yamamura
    • 2
  • M. Nakashima
    • 1
  1. 1.Department of PharmacologyHamamatsu University School of MedicineHamamatsuJapan
  2. 2.Analytical and Metabolic Research LaboratoriesSankyo Co., Ltd.TokyoJapan

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