PULMONARY EXTRACTION AND PHARMACOKINETICS OF PROSTAGLANDIN-E1 DURING CONTINUOUS INTRAVENOUS-INFUSION IN PATIENTS WITH ADULT RESPIRATORY-DISTRESS SYNDROME
PULMONARY EXTRACTION AND PHARMACOKINETICS OF PROSTAGLANDIN-E1 DURING CONTINUOUS INTRAVENOUS-INFUSION IN PATIENTS WITH ADULT RESPIRATORY-DISTRESS SYNDROME
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DOI：
10.1164/ajrccm/137.1.5
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发表时间：
1988-01-01
期刊：
影响因子：
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通讯作者：
VASSAR, MJ
中科院分区：
文献类型：
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作者：
COX, JW;ANDREADIS, NA;VASSAR, MJ
前列腺素E1(PGE1)目前正在进行临床试验，以确定其在成人呼吸窘迫综合征(ARDS)治疗中的有效性。ARDS患者通过持续静脉滴注给药，剂量率高达30 ng/kg/min，连续7天。本研究测定了在此条件下PGE1的肺提取效率和药代动力学。用高效液相色谱法测定了14例ARDS或创伤或脓毒症后有发展为ARDS风险的患者的血浆PGE1水平。给药前血浆PGE1水平低于该方法的检出限(50pg/ml)。剂量率为30 ng/kg/min时，肺动脉和体动脉血浆浓度分别为265~1009pg/ml和50~796pg/ml。PGE1的肺提取率(EP)在0.11~0.90之间变化，且与剂量无关，但依赖于心输出量。这些数据用一级药代动力学方程进行了充分的描述，该方程假定肺是PGE1清除的唯一部位。10例AaPO2/FIO2<510 mm Hg的患者中，9例有EP>；0.7，PGE_1肺固有清除较高(约250 L/分钟)，而4例AaPO_2/FiO2>510 mm Hg的患者，均有EP<；0.6，低固有清除(约37 L/min或以下)。因此，一旦达到严重呼吸衰竭的阈值，ARDS患者肺对PGE1的固有清除量似乎突然下降。
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 1009 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/F1O2 below 510 mm Hg had Ep > 0.7 and high pulmonary intrinsic clearance for PGE1 (ca. 250 L/min), but all 4 patients with AaPO2/FIO2 above 510 mm Hg had Ep < 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.