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Medical > Therapy > Specific treatments

Prostanoids
Aerosolized Iloprost

Because of its short half-life and absent oral bioavailability, epoprostenol has to be administrated by continuous intravenous infusion leading to major problems due to complications of the intravenous lines and the infusion pump. Therefore, stable prostacyclin analogues with longer half-life were developed and studied in large randomized trials using alternative ways of administration such as inhalation (iloprost), continuous subcutaneous infusion (treprostinil), and the oral route (beraprost).

The administration of porstaglandins as an aerosol circumvents most of the aforementioned drawbacks, resulting in a selective effect of the drug on pulmonary vessels. The same principle has already been used with inhalation of nitric oxide (NO), a drug which selectively dilates the pulmonary arteries but has a very short half life and can result in a rebound phenomenon once it is withdrawn. A substantial number of patients with PH (20-30 %) do not respond to NO. Alternatively, inhalative prostacyclin has been used for the treatment of PH and was first published in 1993 in patients with ARDS (Walmrath et al. 1993) and in an animal model of PH (Walmrath et al. 1997). The same group reported the first six patients with PAH treated with inhaled prostacyclin or with its stable analogue, iloprost (Olschewski et al. 1996). In the meantime, many case series have shown that inhaled iloprost is effective in patients with IPAH (Hoeper et al. 2000; Olschewski et al. 2000; Machherndl et al. 2001), PAH due to collagen vascular disease (Olschewski et al. 2000), HIV infection (Stricker et al. 1999; Ghofrani et al. 2004), CTEPH (Olschewski et al. 2000; Machherndl et al. 2001), and PH associated with pulmonary fibrosis (Olschewski et al. 1999; Olschewski et al. 2000). Inhaled iloprost was also successfully used in very severe PH with decompensated right heart function (Olschewski et al. 2000).

Subsequently, a large randomized placebo-controlled trial in 203 patients, the AIR study was conducted (Olschewski et al. 2002). Inhaled iloprost at the median inhaled dose measured at the mouth piece of 30 µg/day (6 to 9 times 2.5-5.0 µg/day was compared with placebo. The combined clinical end point was an improvement in the 6-minute walk distance of at least 10 % and an improvement in the NYHA class of at least one class, and it was met in 17 % of the patients receiving iloprost compared with 5 % of the patients receiving placebo (p = 0.007). The mean increase in the 6-minute walk distance was 36 m compared with placebo, and in the subgroup with PPH 59 m. Only 4 % in the iloprost group did not complete the study compared with 14 % in the placebo group (p = 0.024). There was also a significant improvement in dyspnea score and quality of life. Side effects of iloprost inhalations were generally mild and included increased cough, flushing and jaw pain.

Of note is that the AIR study so far is the only trial that included also patients with CTEPH (overall around 30 % of the study group). In this subgroup a small beneficial effect of inhaled iloprost could be demonstrated, although the difference in the was not significant possibly due to the insufficient statistical power of the subgroup analysis.

References

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