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Prostacyclin metabolites in human plasma

B Rosenkranz, C Fischer, J C Frölich

    Clinical Pharmacology and Therapeutics
    |March 1, 1981
    PubMed
    Summary

    The major breakdown product of prostacyclin (PGI2) in human plasma is 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha). Other circulating metabolites identified include dinor-6, 15-diketo-13, 14-dihydro-PGF1 alpha and its w-oxidized analog.

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    Area of Science:

    • Biochemistry
    • Pharmacology
    • Analytical Chemistry

    Background:

    • Prostacyclin (PGI2) is a crucial vasodilator and inhibitor of platelet aggregation.
    • Understanding PGI2 metabolism in vivo is essential for its therapeutic applications.
    • Previous studies have focused on in vitro hydrolysis, necessitating in vivo metabolite identification.

    Purpose of the Study:

    • To identify and quantify the major metabolites of prostacyclin (PGI2) in human plasma.
    • To characterize the in vivo breakdown products of prostacyclin after intravenous administration.

    Main Methods:

    • Intravenous infusion of tritium-labeled prostacyclin (PGI2) in human subjects.
    • Plasma extraction and separation using high-pressure liquid chromatography (HPLC).
    • Identification of radioactive peaks using gas chromatography-mass spectrometry (GC-MS) after derivatization.

    Main Results:

    • 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) was identified as the major metabolite, accounting for 41.6% of radioactivity.
    • Dinor-6, 15-diketo-13, 14-dihydro-PGF1 alpha was detected as a minor metabolite (6.6% radioactivity).
    • Dinor-6, 15-diketo-13, 14-dihydro-20-carboxyl-PGF1 alpha was also identified (10.1% radioactivity).

    Conclusions:

    • 6-keto-PGF1 alpha is the primary in vivo breakdown product of prostacyclin in human plasma.
    • Dinor-6, 15-diketo-13, 14-dihydro-PGF1 alpha and its w-oxidized analog are also circulating metabolites of PGI2.

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