Sokol R J, Heubi J E, Butler-Simon N, McClung H J, Lilly J R, Silverman A
Department of Pediatrics, University of Colorado School of Medicine, Denver.
Gastroenterology. 1987 Nov;93(5):975-85. doi: 10.1016/0016-5085(87)90559-2.
Treatment of vitamin E deficiency during chronic childhood cholestasis is hampered by the poor intestinal absorption of available oral preparations of vitamin E when bile flow is severely impaired; thus parenteral vitamin E has been the only effective therapy for many children with this problem. We studied the intestinal absorption, efficacy, and safety of a water-soluble oral form of vitamin E, d-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS), in 22 children (7 mo to 19 yr old) with severe cholestasis and vitamin E deficiency who were unresponsive to massive oral doses (100-200 IU/kg.day) of dl-alpha-tocopherol. The results of oral vitamin E tolerance tests showed that TPGS was well absorbed in virtually all study subjects, that TPGS intestinal absorption was superior to that of dl-alpha-tocopherol, and that TPGS absorption in teenage children with chronic cholestasis was similar to that of normal adults. In addition, 1.7% +/- 1.6% (mean +/- SD) of the administered polyethylene glycol 1000 contained in the TPGS was absorbed and excreted in the urine of the 13 subjects analyzed, compared with 3.0% +/- 1.3% in 4 normal adults. A chronic oral dose of 15-25 IU/kg.day of TPGS corrected the biochemical vitamin E deficiency state over 1-19 mo (mean, 10.6 mo) of TPGS therapy. No clinical or biochemical evidence of gastrointestinal, renal, hepatic, or hematologic toxicity was demonstrated. This study suggests that TPGS administered orally in a dose of 15-25 IU/kg.day may be a safe and effective form of vitamin E for prevention and correction of vitamin E deficiency during severe childhood cholestasis.
在儿童慢性胆汁淤积症期间，当胆汁流动严重受损时，可用的口服维生素E制剂肠道吸收较差，这阻碍了维生素E缺乏症的治疗；因此，肠胃外补充维生素E一直是许多患有此问题儿童的唯一有效疗法。我们研究了一种水溶性口服维生素E制剂，即d-α-生育酚聚乙二醇1000琥珀酸酯（TPGS），对22名患有严重胆汁淤积症和维生素E缺乏症且对大剂量口服dl-α-生育酚（100 - 200 IU/kg·天）无反应的儿童（年龄从7个月至19岁）的肠道吸收、疗效及安全性。口服维生素E耐受性测试结果表明，几乎所有研究对象对TPGS的吸收良好，TPGS的肠道吸收优于dl-α-生育酚，并且患有慢性胆汁淤积症的青少年对TPGS的吸收与正常成年人相似。此外，在分析的13名受试者尿液中，TPGS所含的1.7%±1.6%（均值±标准差）的聚乙二醇1000被吸收并排出，而4名正常成年人中的这一比例为3.0%±1.3%。每天口服15 - 25 IU/kg的TPGS，在1 - 19个月（平均10.6个月）的TPGS治疗后，纠正了生化维生素E缺乏状态。未发现胃肠道、肾脏、肝脏或血液学毒性的临床或生化证据。这项研究表明，每天口服剂量为15 - 25 IU/kg的TPGS可能是预防和纠正儿童严重胆汁淤积症期间维生素E缺乏症的一种安全有效的维生素E形式。
