Iloprost is a second generation structural analog of prostacyclin (PGI) with about ten-fold greater potency than the first generation stable analogs, typified by carbaprostacyclin.1 Iloprost binds with equal affinity to the human recombinant IP and EP1 receptors with a Ki of 11 nM.2 Iloprost constricts the isolated guinea pig ilium and fundus circular smooth muscle (an EP1 receptor preparation) as strongly as prostaglandin E2 (PGE2) itself.3 Iloprost inhibits the ADP, thrombin, and collagen-induced aggregation of human platelets with an ED50 of about 13 nM.1 In whole animals, iloprost acts as a vasodilator, hypotensive, antidiuretic, and prolongs bleeding time.4 It has been evaluated in several human clinical studies as a treatment for idiopathic pulmonary hypertension.5,6 In these studies, an aerosolized dose of 30 µg/day was effective, and doses as high as 150 µg/day for up to a year were well tolerated.
1
Schrör, K., Darius, H., Matzky, R., et al. The antiplatelet and cardiovascular actions of a new carbacyclin derivative (ZK36374) - equipotent to PGI2in vitro. Naunyn Schmiedebergs Arch Pharmacol316252-255(1981).
2
Abramovitz, M., Adam, M., Boie, Y., et al. The utilization of recombinant prostanoid receptors to determine the affinities and selectivities of prostaglandins and related analogs. Biochim Biophys Acta1483285-293(2000).
3
Sheldrick, R.L.G., Coleman, R.A., and Lumley, P. Iloprost - a potent EP1- and IP-receptor agonist. Br J Pharmacol94334P(1988).
5
Hoeper, M.M., Schwarze, M., Ehlerding, S., et al. Long-term treatment of primary pulmonary hypertension with aerosolized iloprost, a prostacyclin analogue. N Engl J Med3421866-1870(2000).
6
Olschewski, H., Simonneau, G., Galié, N., et al. Inhaled iloprost for severe pulmonary hypertension. N Engl J Med347(5)322-329(2002).
Schrör, K., Darius, H., Matzky, R., et al. The antiplatelet and cardiovascular actions of a new carbacyclin derivative (ZK36374) - equipotent to PGI2in vitro. Naunyn Schmiedebergs Arch Pharmacol316252-255(1981).
Sheldrick, R.L.G., Coleman, R.A., and Lumley, P. Iloprost - a potent EP1- and IP-receptor agonist. Br J Pharmacol94334P(1988).
Abramovitz, M., Adam, M., Boie, Y., et al. The utilization of recombinant prostanoid receptors to determine the affinities and selectivities of prostaglandins and related analogs. Biochim Biophys Acta1483285-293(2000).
Hoeper, M.M., Schwarze, M., Ehlerding, S., et al. Long-term treatment of primary pulmonary hypertension with aerosolized iloprost, a prostacyclin analogue. N Engl J Med3421866-1870(2000).
Olschewski, H., Simonneau, G., Galié, N., et al. Inhaled iloprost for severe pulmonary hypertension. N Engl J Med347(5)322-329(2002).