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European Journal of Clinical Pharmacology

, Volume 30, Issue 1, pp 61–68 | Cite as

Pharmacokinetics and pharmacodynamics of the prostacyclin analogue iloprost in man

  • W. Krause
  • Th. Krais
Originals

Summary

Plasma levels of the prostacyclin analogue, iloprost, were measured by antibody/GC/MS in healthy male volunteers given 1 and 3 ng/kg per min i.v. for 45 min, and 1 µg/kg p.o. Following i.v. infusion, the steady-state plasma levels of iloprost were strictly dose-dependent (46±8 pg/ml and 135±24 pg/ml). The disposition was biphasic with half-lives of 3–4 min and 0.5 h. After oral administration, absorption of the drug was extremely rapid, the maximum plasma level of 251±32 pg/ml being achieved after 10±6 min. The bioavailability was 16±4%. Platelet aggregation induced by 2 µM ADP was reduced by 53% and 68% at the end of the two different infusions, and by 68% 15 min after p.o. administration. The ex-vivo inhibition of platelet aggregation by iloprost was not affected by preceding drug treatment. The cAMP content of platelets was increased by a factor of 2.5 at the end of the infusions and to a lesser extent 15 min after oral dosing. A slight increase in heart rate occurred during the infusion and within 30 min after oral administration; blood pressure was virtually unaffected. Except for transient side-effects (facial flush and headache) no adverse reactions were observed.

Key words

iloprost prostacyclin analogue pharmacokinetics platelet aggregation healthy male volunteers adverse effects 

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Copyright information

© Springer-Verlag 1986

Authors and Affiliations

  • W. Krause
    • 1
  • Th. Krais
    • 1
  1. 1.Schering AGBerlinGermany

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