Galbraith R A, Drummond G S, Kappas A
Rockefeller University Hospital, New York, NY 10021.
Pediatrics. 1992 Feb;89(2):175-82.
The heme oxygenase inhibitor tin-mesoporphyrin was used to moderate hyperbilirubinemia in two 17-year-old boys with Crigler-Najjar type I syndrome. Both patients had histories of recent, progressive neurological deterioration and plasma bilirubin concentrations on admission to the hospital were 34.5 and 28.5 mg/dL. Throughout hospitalization lasting more than 400 days, both patients underwent 10 hours of phototherapy nightly and consumed constant weight-maintaining diets. They were treated with intermittent plasmapheresis and two periods of tin-mesoporphyrin therapy comprising, in the first study period, 40 doses of 0.5 mumol/kg body weight and in the second study period, 70 doses of 1.0 mumol/kg body weight. Plasma bilirubin concentrations were decreased in both patients to varying degrees as was the rebound hyperbilirubinemia which occurs after plasmapheresis. The prolonged treatments with the inhibitor were well-tolerated and no progression of the preexisting neurological impairments occurred during the clinical trials. The results of this study suggest that the clinical application of an effective heme oxygenase inhibitor can provide a potentially useful, pharmacological adjunct to presently available therapeutic modalities for controlling episodes of acute, severe jaundice in this but lethal disorder.
血红素加氧酶抑制剂锡-中卟啉被用于治疗两名患有Ⅰ型克里格勒-纳贾尔综合征的17岁男孩的高胆红素血症。两名患者近期均有进行性神经功能恶化病史，入院时血浆胆红素浓度分别为34.5和28.5mg/dL。在持续超过400天的住院期间，两名患者每晚均接受10小时的光疗，并采用维持体重的固定饮食。他们接受了间歇性血浆置换治疗以及两个阶段的锡-中卟啉治疗，在第一个研究阶段，给予40剂0.5μmol/kg体重的药物，在第二个研究阶段，给予70剂1.0μmol/kg体重的药物。两名患者的血浆胆红素浓度均有不同程度降低，血浆置换后出现的反弹性高胆红素血症也有所减轻。抑制剂的长期治疗耐受性良好，在临床试验期间，先前存在的神经功能损害未出现进展。本研究结果表明，有效血红素加氧酶抑制剂的临床应用可为目前控制这种致命性疾病急性重度黄疸发作的现有治疗方式提供一种潜在有用的药理学辅助手段。
