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 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.