A phase I study of oxidized raffinose cross-linked human hemoglobin
A phase I study of oxidized raffinose cross-linked human hemoglobin
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DOI：
10.1097/00003246-200007000-00017
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发表时间：
2000-07-01
影响因子：
8.8
通讯作者：
Greenburg, AG
中科院分区：
文献类型：
--
作者：
Carmichael, FJL;Ali, ACY;Greenburg, AG
目的：评价氧化棉子糖交联人血红蛋白Hemolink在正常健康志愿者中的安全性。设计：随机、安慰剂对照、双盲研究。设置：合同研究组织的临床研究机构。患者：42名健康成年男性志愿者，其中33名接受Hemolink，干预：在第1天静脉内输注作为10%（w/v）溶液的氧化棉子糖交联和聚合血红蛋白，剂量为0.025-0.6 g/kg或等体积的乳酸林格氏溶液，并且在临床设施中监测受试者3天，随访少于或等于6周。通过血流动力学、心电图、肺功能和临床化学measurements. Measures和主要结果：给予1.7-42 g血红蛋白的剂量，未发现严重不良事件。在剂量>0.4 g/kg时，在一些受试者中观察到中度至重度腹痛，并使用平滑肌松弛剂缓解。平均动脉压呈剂量依赖性升高，在0.1 g/kg剂量下，平台期约为基线以上14%。心率下降，心电图未见异常，呼吸功能未受影响。血清胆红素呈剂量依赖性增加，在大于或等于0.4 g/kg的剂量下，数值高于正常上限。在一些患者中观察到天冬氨酸转氨酶和丙氨酸转氨酶的小幅升高，而碱性磷酸酶和γ-谷氨酰转移酶保持在正常范围内。33例接受Hemolink治疗的患者中有31例的血清淀粉酶浓度正常，而33例患者中有21例的脂肪酶浓度在正常范围内。LDH以剂量依赖性方式增加。2例患者肌酸激酶浓度升高，肌酸激酶-MB质量分数正常。所有血液学变量均在正常范围内。Hemolink的低聚物（>64 kDa）级分的半衰期为18-20小时。结论：剂量小于或等于0.6 g/kg的氧化棉子糖交联血红蛋白（Hemolink）在健康志愿者中耐受良好，无器官功能障碍证据。进一步研究其在外科和创伤环境中的潜在用途似乎是必要的。
Objective: To evaluate the safety of oxidized-raffinose crosslinked human hemoglobin, Hemolink, in normal healthy volunteers.Design: Randomized, placebo-controlled, double-blind study.Setting: Clinical research facility of a contract research organization.Patients: Forty-two healthy adult male volunteers of which 33 received Hemolink,Interventions: Oxidized-raffinose cross-linked and polymerized hemoglobin as a 10% (w/v) solution, in doses of 0.025-0.6 g/kg or an equivalent volume of lactated Ringer's solution, was infused intravenously on day 1, and subjects were monitored for 3 days in the clinical facility with less than or equal to 6 wks follow-up. Major organ function was assessed pre- and postinfusion, by hemodynamic, electrocardiographic, pulmonary function, and clinical chemistry measurements.Measurements and Main Results: Doses of 1.7-42 g of hemoglobin were administered with no serious adverse events noted. Abdominal pain of moderate to severe intensity was seen in some subjects at doses >0.4 g/kg and was alleviated with smooth muscle relaxants. There was a dose-dependent increase in mean arterial pressure with a plateau of approximately 14% above baseline at 0.1 g/kg. There was a concomitant reduction in heart rate, with no electrocardiographic abnormalities found. Respiratory function was not affected. There was a dose-dependent increase in serum bilirubin with values above the upper limit of normal at doses of greater than or equal to 0.4 g/kg. Small increases in aspartate aminotransferase and alanine aminotransferase were noted in some patients, whereas alkaline phosphatase and gamma-glutamyltransferase remained in the normal range. Serum amylase concentrations were normal in 31 of 33 patients receiving Hemolink, whereas lipase was within the normal range in 21 of 33 patients. LDH was increased in a dose-dependent fashion. Two patients had increased creatine kinase concentrations, with a normal creatine kinase-MB mass fraction. All hematologic variables were within the normal range. The half-life of the oligomeric (>64 kDa) fraction of Hemolink was 18-20 hrs,Conclusion: Oxidized-raffinose cross-linked hemoglobin, Hemolink, at doses less than or equal to 0.6 g/kg were well tolerated in healthy volunteers with no evidence of organ dysfunction. Further investigation of its potential use in surgical and trauma settings appears warranted.