Pharmacological activity and local and systemic tolerance of topically applied iloprost

The chemically stable prostacyclin derivative iloprost (CAS 73873-87-7) infused intravenously induces vasodilation and inhibits platelet aggregation. Numerous clinical studies have shown that iloprost is beneficial in the treatment of obliterative arterial disease. As a topical therapy would have considerable advantages, the pharmacological activity and the tolerance of the drug was evaluated in several studies which included 73 healthy volunteers. The drug was tested in different galenical formulations: aqueous solution, various hydrogels and a fatty ointment. They were applied to intact as well as experimentally damaged (stripped) skin. The pharmacodynamic effects were determined by visual assessment, colorimetry and laser Doppler velocimetry. Moreover, the volunteers were monitored for systemic side effects including changes in blood and urine. After the solution was applied under occlusion, iloprost induced erythema at dose levels of at least 50/25 ng/cm2 (intact/stripped skin). Applied to intact skin, erythema lasted for up to 5 days. When the drug was applied to stripped skin the effect was shorter (24 h). Following low doses, erythema was confined predominantly to the follicles whereas homogeneous redness was induced by higher iloprost doses. Thus penetration seems to occur in particular via the follicles with the horny layer acting as a penetration barrier and as a drug reservoir. High doses (400/150 ng/cm2) induced edema in all cases when applied to intact/stripped skin. When applied to large areas of the skin, increased iloprost serum levels (< or = 80 pg/ml) as well as systemic side effects (inhibition of platelet function, flush, headache) were observed. Tachyphylaxia did not develop after the application of 25 micrograms/100 cm2 once daily for 60 days.(ABSTRACT TRUNCATED AT 250 WORDS)