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Schermuly, R.T. et al.

Schermuly, Schulz, Ghofrani, Meidow, Rose, Roehl, Weissmann, Hildebrand, Kurz, Grimminger, Walmrath, Seeger,

Pharmacokinetics and metabolism of infused versus inhaled iloprost in isolated rabbit lungs.

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.[1]

References

Pharmacokinetics and metabolism of infused versus inhaled iloprost in isolated rabbit lungs. Schermuly, R.T., Schulz, A., Ghofrani, H.A., Meidow, A., Rose, F., Roehl, A., Weissmann, N., Hildebrand, M., Kurz, J., Grimminger, F., Walmrath, D., Seeger, W. J. Pharmacol. Exp. Ther. (2002) [Pubmed]

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