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Prostaglandin E1 (PGE1) is currently being evaluated in clinical trials to determine its usefulness in the treatment of adult respiratory distress syndrome (ARDS). The drug is administered to ARDS patients by continuous intravenous infusion at dosage rates of up to 30 ng/kg/min for 7 days. The present study was conducted to determine the pulmonary extraction efficiency and pharmacokinetics of PGE1 under these conditions. Plasma levels of PGE1 were determined by high performance liquid chromatography in 14 patients who either had ARDS or were considered to be at risk of developing ARDS following trauma or sepsis. Predose plasma levels of PGE1 were below the detection limit of the assay (50 pg/ml). At a dosage rate of 30 ng/kg/min, pulmonary arterial and systemic arterial plasma levels ranged from 265 to 1,009 pg/ml and 50 to 796 pg/ml, respectively. The pulmonary extraction ratio (Ep) of PGE1 varied from 0.11 to 0.90 and was independent of dose but dependent on cardiac output. The data were adequately described by first-order pharmacokinetic equations which assumed that the lung was the only site of PGE1 clearance. Nine of 10 patients with AaPO2/FlO2 below 510 mm Hg had Ep greater than 0.7 and high pulmonary intrinsic clearance for PGE1 (ca. 250 L/min), but all 4 patients with AaPO2/FlO2 above 510 mm Hg had Ep less than 0.6 and low intrinsic clearance (ca. 37 L/min or less). The intrinsic clearance of the lung for PGE1 in ARDS patients therefore appears to decrease abruptly once a threshold of severe respiratory failure is achieved.

Most previous reports suggesting beneficial effects ofprostaglandin E1 (PGEI) have been retrospective and uncontrolled. Therefore, this study was undertaken to assess the efficacy of PGE1 in the treatment ofischemic ulcers in patients with peripheral vascular occlusive disease (PVOD). One hundred twenty patients with one to three ischemic ulcers not healing for 3 weeks with standard care were randomized to receive either PGE1 (20 ng/kg/min) or a placebo for 72 hours through a central venous catheter. Ulcers were measured and photographed, and the rest pain was evaluated before and after infusion and at 1-and 2-month follow-up intervals. Fifty-seven patients with 95 ulcers received PGE1. Seventeen ulcers healed (18%); 22 ulcers decreased in size (23%); 37 ulcers remained unchanged or increased in size (39%); five new ulcers developed during the study (5%); and 14 ulcers had inadequate follow-up (15%). Sixty-three patients with 115 ulcers received a placebo. Nineteen ulcers healed (16%); 38 ulcers decreased in size (33%); 45 ulcers remained unchanged or increased in size (39%); three new ulcers developed during the study (3%); and 10 ulcers had inadequate follow-up (9%). None of the above differences between the drug-treated group and the placebo-treated group was statistically significant. This study did not demonstrate efficacy for intravenously administered PGE~ in the healing of ischemic ulcers in patients with PVOD. (J VASC SURG 1984; 1:160-70.) The treatment of ischemic ulcers and rest pain of the lower extremities continues to be one of the most important problems in the management of peripheral vascular occlusive disease. This is especially true for those patients in whom lower extremity revascularization is not indicated or in whom conventional revascularization with bypass techniques is judged unlikely to be of long-term benefit. Treatment with various vasodilators has been shown to be ineffective and may in fact increase the degree of