Pharmacokinetics and pharmacodynamics of the prostacyclin analogue iloprost in man.
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 microgram/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 microM 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.
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D000284:Administration, Oral; D000328:Adult; D001682:Biological Availability; D001774:Blood Chemical Analysis; D001794:Blood Pressure / Q000187:drug effects; D002317:Cardiovascular Agents / Q000009:adverse effects / Q000378:metabolism / Q000494:pharmacology*; D000242:Cyclic AMP / Q000097:blood; D004562:Electrocardiography; D011464:Epoprostenol / Q000009:adverse effects / Q000378:metabolism / Q000494:pharmacology*; D006207:Half-Life; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D016285:Iloprost; D007263:Infusions, Parenteral; D007700:Kinetics; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects; D012119:Respiration / Q000187:drug effects
D002317:Cardiovascular Agents; D011464:Epoprostenol; D000242:Cyclic AMP; D016285:Iloprost