Pharmacokinetics of iloprost in patients with severe peripheral arterial occlusive disease

The pharmacokinetics of iloprost were studied in 12 hospitalized patients suffering from severe peripheral arterial occlusive disease (PAOD) stages III or IV according to Fontaine. The patients were 8 males and 4 females aged from 49 to 83 years. Apart from PAOD, several other concomitant diseases were present, e.g. myocardial and/or renal insufficiency, diabetes and hypertension. Patients were treated daily with i.v. infusions of iloprost at dosages of 1.0-3.3 ng/kg/min over a period of 4 to 6 h. Dose-normalized steady-state plasma levels ranged from 39 to 100 pg/ml (65 +/- 20 pg/ml). The total clearance accounted for 16 +/- 5 ml/min/kg. Post-infusion disposition in the plasma was biphasic with half-lives of 4 +/- 2 min and 37 +/- 8 min. The plasma level profiles obtained on days 4 and 14 of treatment in 3 patients were similar. Sex specific kinetic differences were not observed. In comparison to healthy volunteers, studied in an earlier trial, total clearance was slightly lower and consequently steady state levels were increased (p less than 0.05) in PAOD patients. Half-lives in the plasma were not significantly different.