PT  - JOURNAL ARTICLE
AU  - Ralph Theo Schermuly
AU  - Andreas Schulz
AU  - Hossein Ardeschir Ghofrani
AU  - Arne Meidow
AU  - Frank Rose
AU  - Axel Roehl
AU  - Norbert Weissmann
AU  - Michael Hildebrand
AU  - Julia Kurz
AU  - Friedrich Grimminger
AU  - Dieter Walmrath
AU  - Werner Seeger
TI  - Pharmacokinetics and Metabolism of Infused versus Inhaled Iloprost in Isolated Rabbit Lungs
AID  - 10.1124/jpet.303.2.741
DP  - 2002 Nov 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 741--745
VI  - 303
IP  - 2
4099  - http://jpet.aspetjournals.org/content/303/2/741.short
4100  - http://jpet.aspetjournals.org/content/303/2/741.full
SO  - J Pharmacol Exp Ther2002 Nov 01; 303
AB  - 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 ∼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 ∼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 β-oxidation, and more rapid appearance of dinor- and tetranoriloprost is noted for the inhalative as compared with the intravascular route of iloprost administration. The American Society for Pharmacology and Experimental Therapeutics