Preliminary evaluation of AS-013 (prodrug of prostaglandin E₁) administration for chronic peripheral arterial occlusive disease

Abstract

Prostaglandin E₁ (PGE₁) and one of its prodrugs, AS-013, were formulated in lipid microspheres (lipo-PGE₁ and lipo-AS, respectively), and their acute clinical efficacy and safety were compared in a randomized, placebo-controlled, single-blind test. Lipo-PGE₁ (10 μg), lipo-AS (5 μg), or an inactive placebo was intravenously administered to human subjects once daily for 3 days. The acute efficacy of lipo-PGE₁ and lipo-AS was each quantitatively assessed in male patients with chronic peripheral arterial occlusive diseases (PAOD) by measuring ankle brachial pressure, skin temperature, transcutaneous oxygen pressure (tcPO₂), transcutaneous carbonic dioxide pressure, and cutaneous blood flow (BF) with a laser Doppler flowmeter during and after administration of each drug. Informed consent was obtained from all patients. Laboratory data did not suggest any adverse effect of lipo-AS administration, which significantly improved tcPO₂ and BF, suggesting that the microhemorrheological effects of lipo-AS are of potential therapeutic value in the treatment of PAOD.