Iloprost is a potent
prostacyclin analog, which has been shown to exert beneficial effects in several vascular disorders. Inhalation of aerosolized
iloprost was found to cause selective pulmonary vasodilatation, and this approach is under current investigation for treatment of chronic
pulmonary hypertension. The present study investigated pharmacokinetics and metabolism of aerosolized
iloprost in isolated
buffer-perfused rabbit lungs, compared with intravascular administration of the
prostanoid. After
buffer admixture of
iloprost, a steady decline of perfusate concentrations of the intact
prostanoid was noted (half-life approximately 3.5 h), mostly attributable to progressive metabolism to
dinor- and tetranoriloprost. Inhaled
iloprost rapidly entered the intravascular compartment, with peak
buffer concentrations being noted after 30 min (bioavailability approximately 63%). Compared with infused
iloprost, significantly more rapid metabolism to
dinor- and tetranoriloprost was noted for
iloprost administered via the inhalative route of application. However, the percentage of the nebulized agent that enters the intravascular space as intact
iloprost displays the same clearance rate as directly perfusate-admixed
prostanoid. We conclude that a high percentage of inhaled
iloprost rapidly enters the intravascular compartment in intact rabbit lungs. The lung is capable of metabolizing
iloprost via beta-oxidation, and more rapid appearance of
dinor- and tetranoriloprost is noted for the inhalative as compared with the intravascular route of
iloprost administration.