Pharmacokinetics of oral iloprost in patients with Raynaud's phenomenon secondary to systemic sclerosis.

Iloprost is a chemically stable, pharmacologically highly potent prostacyclin-minietic. The therapeutic efficacy of the intravenous preparation was proven in patients with peripheral arterial occlusive disease or with Raynaud's phenomenon (RP). Recently, a sustained release oral preparation was developed for outpatient therapy. The purpose of the current study was to investigate whether the oral drug has a different pharmacokinetic profile in patients with RP secondary to systemic sclerosis (SSc) in comparison with healthy volunteers. Ten patients with RP secondary to SSc and 10 healthy volunteers (matched for age and sex) participated. Oral iloprost 50 microg was given twice daily for 8 days with dosing intervals of 5 h and plasma levels were taken over 10 h on Day 1 and 8. Plasma levels of iloprost were determined by a validated specific and sensitive radio-immunoassay. Compared with healthy volunteers, patients with SSc exhibited higher AUC values (by mean factors of 2. 1 and 2.0 on Day 1 and 8) and maximum plasma levels (by mean factors of 1.6 and 1.8 on Day 1 and 8). The increased systemic iloprost exposure was observed after both daily doses and on both monitored study days. Mean AUC values did not show accumulation over the 8 days. These findings are in agreement with a reduced total clearance of iloprost given by i.v. route in SSc patients compared to healthy volunteers, although no participant with severe renal impairment was included. A weak but significant correlation was found between individual creatinine clearance and AUC values. In conclusion, RP secondary to SSc is associated with an increased systemic iloprost exposure which is probably caused by changes of the metabolic clearance of iloprost. These effects cannot be explained by changes of renal function alone.