On the Metabolism and Pharmacokinetics of Prostaglandin E1 Administered by Intra-arterial or Intravenous Infusions

  • B. A. Peskar
  • W. H. Hesse
  • W. Rogatti
  • G. Rudofsky
Conference paper

Abstract

Both intra-arterial and intravenous infusions of prostaglandin (PG)E1 have been used in the treatment of peripheral arterial occlusive disease [17]. However, only few data on the pharmacokinetics and metabolic fate of PGE1 in man are available so far [4, 6, 7, 10, 16]. We have recently described [13] plasma levels of PGE1 and its circulating metabolite 15-keto-13,14-dihydro-PGE1 (KH2PGE1) in the cubital vein of healthy volunteers receiving PGE1 infusions into the contralateral cubital vein. We have now compared plasma levels of PGE1 and KH2PGE1 in healthy volunteers treated with either intra-arterial or intravenous infusions of PGE1. Furthermore, since the initial metabolites of PGE1 15-keto-PGE1 and KH2PGE1 have only negligible biological activity [1, 18], we have additionally determined the occurrence of 13,14-dihydro-PGE1 (H2PGE1), a biologically active metabolite [1, 3, 18], during intravenous PGE1 infusions in patients with peripheral arterial occlusive disease [12].

Keywords

HPLC Syringe Angiotensin Dehydration Prostaglandin 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Änggård E (1966) The biological activities of three metabolites of prostaglandin E1 Acta Physiol Scand 66: 509–510PubMedCrossRefGoogle Scholar
  2. 2.
    Bothwell W, Verburg M, Wynalda M, Daniels EG, Fitzpatrick FA (1982) A radioimmunoassay for the unstable pulmonary metabolites of prostaglandin and E2: an indirect index of their in vivo disposition and pharmacokinetics. J. Pharmacol Exp Ther 220: 229–235PubMedGoogle Scholar
  3. 3.
    Braun M, Ney P, Szymanski Ch, Bruch L, Schrbr K (1991) 13,14-dihydro-PGE1, a potent inhibitor of human platelet and neutrophil activation. Br J Pharmacol 102: 90 PGoogle Scholar
  4. 4.
    Cox JW, Andreadis VA, Bone RC, Maunder RJ, Pullen RH, Ursprung JJ, Vassar MJ (1988) Pulmonary extraction and pharmacokinetics of prostaglandin E1 during continous intravenous infusion in patients with adult respiratory distress syndrome. Am Rev Respir Dis 137: 5–12PubMedCrossRefGoogle Scholar
  5. 5.
    Diekmann JM, Jobke A, Peskar BA, Hertting G (1977) Angiotensin II-Induced contractions of rabbit splenic capsular strips and release of prostaglandins. Use of radioimmunoassays for prostaglandins E1 and E2. Naunyn-Schmiedebergs Arch Pharmacol 297: 177–183PubMedCrossRefGoogle Scholar
  6. 6.
    Gillis CN, Pitt BR, Wiedemann HP, Hammond GL (1986) Depressed prostaglandin E1 and 5-hydroxytryptamine removal in patients with adult respiratory distress syndrome. Am Rev Respir Dis 134: 739–744PubMedGoogle Scholar
  7. 7.
    Golub M, Zia P, Matsuno M, Horton R (1975) Metabolism of prostaglandin A1 and E1 in man. J Clin Invest 56: 1404–1410PubMedCrossRefGoogle Scholar
  8. 8.
    Hesse WH, Schweer H, Seyberth HW, Peskar BA (1990) Separation and determination of prostaglandin E1 metabolites by high-performance liquid chromatography. J Chromatogr 533: 159–165PubMedCrossRefGoogle Scholar
  9. 9.
    Hubbard W, Watson JT (1976) Determination of 15-keto-13,14-dihydro metabolites of PGE2 and PGF2α in plasma using high performance liquid chromatography and gas chromatography-mass spectrometry. Prostaglandins 12: 21–36PubMedCrossRefGoogle Scholar
  10. 10.
    Leonhardt A, Kühl PG, Schweer H, Wolf D, Seyberth HW (1989) Pharmacologically active levels of PGE1 in neonates with congenital heart disease. Acta Paediatr Scand 78: 853–857PubMedCrossRefGoogle Scholar
  11. 11.
    Peskar BM, Gunther B, Steffens Ch, Kröner EE, Peskar BA (1980) Antibodies against dehydration products of 15-keto-13,14-dihydro-prostaglandin E2. FEBS Lett 115: 123–126PubMedCrossRefGoogle Scholar
  12. 12.
    Peskar BA, Hesse WH, Rogatti W, Diehm C, Rudofsky G, Schweer H, Seyberth HW (1991) Formation of 13,14-dihydro-prostaglandin Ex during intravenous infusions of prostaglandin E1 in patients with peripheral arterial occlusive disease. Pro-staglandins 41: 225–228Google Scholar
  13. 13.
    Peskar BA, Cawello W, Rogatti W, Rudofsky G. On the metabolism of prostaglandin E1 administered intravenously to human volunteers. J Physiol Pharmacol (in press)Google Scholar
  14. 14.
    Samuelsson B, Green K (1974) Endogenous levels of 15-keto-dihydro-prostaglandins in human plasma. Biochem Med 11: 298–303PubMedCrossRefGoogle Scholar
  15. 15.
    Simmet T, Peskar BA (1988) Prostaglandin and arterial occlusive disease: pharmacological considerations. Eur J Clin Invest 18: 549–554PubMedCrossRefGoogle Scholar
  16. 16.
    Simmet T, Peskar BA, Wolf HRD (1986) On the metabolism of prostaglandin Ex in patients suffering from arterial occlusive disease. In: Sinzinger H, Rogatti W (eds) Prostaglandin E1 in atherosclerosis. Springer, Berlin Heidelberg New York, pp 8–12Google Scholar
  17. 17.
    Sinzinger H, Virgolini I, O’Grady J (1989) Clinical trials of PGE1, PGI2 and mimetics in patients with peripheral vascular disease. In: Schrör K, Sinzinger H (eds) Prostaglandins in clinical research. Liss, New York, pp 85–96Google Scholar
  18. 18.
    Westwick J (1976) The effect of pulmonary metabolites of prostaglandins E1, E2 and F2α on ADP-induced aggregation of human and rabbit platelets. Br J Pharmacol 58: 297 PGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1991

Authors and Affiliations

  • B. A. Peskar
  • W. H. Hesse
  • W. Rogatti
  • G. Rudofsky

There are no affiliations available

Personalised recommendations