口服生育酚聚乙二醇1000琥珀酸酯可纠正或预防慢性胆汁淤积症儿童的维生素E缺乏症。

Oral Tocofersolan Corrects or Prevents Vitamin E Deficiency in Children With Chronic Cholestasis.

作者信息

Thébaut Alice, Nemeth Antal, Le Mouhaër Jeannie, Scheenstra René, Baumann Ulrich, Koot Bart, Gottrand Fredéric, Houwen Roderick, Monard Laure, de Micheaux Sylvie Lafaye, Habes Dalila, Jacquemin Emmanuel

机构信息

*Pediatric Hepatology and Pediatric Liver Transplantation Unit, National Reference Centre for biliary atresia, Assistance Publique-Hôpitaux de Paris, Université Paris Sud, Hepatinov, Le Kremlin-Bicêtre, France †Center for Inherited metabolic Diseases, Karolinska University Hospital Solna, Stockholm, Sweden ‡Medical Department, Orphan Europe, Puteaux, France §Beatrix Childrens Hospital, University Medical Center Groningen, Groningen, The Netherlands ||Division of Paediatric Gastroenterology and Hepatology, Children's Hospital, Hannover Medical School, Hannover, Germany ¶Department of Paediatric Gastroenterology and Hepatology, Academisch Medisch Centrum, Amsterdam, The Netherlands #Department of Pediatric Gastroenterology and Hepatology, CHRU de Lille, Hôpital Jeanne de Flandre, Lille, France **Wilhelmina Childrens Hospital, University Medical Center Utrecht, Utrecht, The Netherlands ††INSERM U1174, Université Paris-Sud, Orsay, France.

出版信息

J Pediatr Gastroenterol Nutr. 2016 Dec;63(6):610-615. doi: 10.1097/MPG.0000000000001331.

DOI:10.1097/MPG.0000000000001331

PMID:27429423

Abstract

OBJECTIVES

D-Alpha-tocopheryl polyethylene glycol 1000 succinate (Tocofersolan, Vedrop), has been developed in Europe to provide an orally bioavailable source of vitamin E in children with cholestasis. The aim was to analyze the safety/efficacy of Vedrop in a large group of children with chronic cholestasis.

METHODS

Two hundred seventy-four children receiving Vedrop for vitamin E deficiency or for its prophylaxis were included from 7 European centers. Median age at treatment onset was 2 months and median follow-up was 11 months. Vedrop was prescribed at a daily dose of 0.34 mL/kg (25 IU/kg) of body weight. Three methods were used to determine a sufficient serum vitamin E status: vitamin E, vitamin E/(total cholesterol), vitamin E/(total cholesterol + triglycerides).

RESULTS

Before Vedrop therapy, 51% of children had proven vitamin E deficiency, 30% had normal vitamin E status and 19% had an unknown vitamin E status. During the first months of treatment, vitamin E status was restored in the majority of children with insufficient levels at baseline (89% had a normal status at 6 months). All children with a normal baseline vitamin E status had a normal vitamin E status at 6 months. Among children with an unknown vitamin E status at baseline, 93% had a normal vitamin E status at 6 months. A sufficient vitamin E status was observed in 80% of children with significant cholestasis (serum total bilirubin >34.2 μmol/L). No serious adverse reaction was reported.

CONCLUSIONS

Vedrop seems a safe and effective oral formulation of vitamin E that restores and/or maintains sufficient serum vitamin E level in the majority of children with cholestasis, avoiding the need for intramuscular vitamin E injections.

摘要

目的

聚乙二醇1000琥珀酸酯维生素E（生育酚聚乙二醇1000琥珀酸酯，Vedrop）已在欧洲研发出来，用于为胆汁淤积症儿童提供口服生物可利用的维生素E来源。目的是分析Vedrop在一大群慢性胆汁淤积症儿童中的安全性/有效性。

方法

从7个欧洲中心纳入了274名因维生素E缺乏或用于预防而接受Vedrop治疗的儿童。治疗开始时的中位年龄为2个月，中位随访时间为11个月。Vedrop的处方剂量为每日0.34 mL/kg（25 IU/kg）体重。使用三种方法来确定足够的血清维生素E状态：维生素E、维生素E/（总胆固醇）、维生素E/（总胆固醇+甘油三酯）。

结果

在Vedrop治疗前，51%的儿童已证实维生素E缺乏，30%的儿童维生素E状态正常，19%的儿童维生素E状态未知。在治疗的头几个月，大多数基线水平不足的儿童的维生素E状态得到恢复（89%在6个月时状态正常）。所有基线维生素E状态正常的儿童在6个月时维生素E状态均正常。在基线时维生素E状态未知的儿童中，93%在6个月时维生素E状态正常。在80%的严重胆汁淤积症儿童（血清总胆红素>34.2 μmol/L）中观察到足够的维生素E状态。未报告严重不良反应。