Dev Pharmacol Ther. 1991;16(1):13-21.
Vitamin E (alpha-toxopherol) is widely used, at different dosages and schedules and in different formulations, in neonatal intensive care units to prevent intraventricular hemorrhage, retrolental fibroplasia, bronchopulmonary dysplasia and hemolytic anemia of preterm infants. As part of a wider project to assess the effect of vitamin E, the present study was designed to determine whether the only intramuscular formulation available today in Italy and in other European countries (olive oil solution), and widely used in all Italian neonatal intensive care units according to a standard schedule, achieves and maintains suggested therapeutic levels, compared to the colloidal aqueous solution used in clinical trials in England and Canada, which contained the acetate ester of alpha-tocopherol and as used in the USA, which contained the free tocopherol, but is not yet available in Italy. Forty-four babies, of less than 32 weeks' gestation, 670-1,800 g birth weight, were randomly allocated to one of the two formulations. We gave 20 mg/kg of vitamin E intramuscularly on 3 consecutive days starting within 8 h of birth (day 0), 24 and 48 h later (days 1 and 2). Blood, plasma, red blood cells after transfusions and milk were sampled up to the sixth day of life. Clinical data were collected up to discharge from the neonatal intensive care unit. Plasma concentrations of vitamin E (free tocopherol) averaged 1.1 at 24 h and 3.3 mg/dl at 72 h after the colloidal aqueous solution, and were about 6 times lower after the oil solution. Plasma vitamin E levels did not rise above baseline after injection of the olive oil preparation. The acetate ester of vitamin E was measured only after use of the colloidal aqueous preparation, and the highest plasma concentration averaged 1.01 mg/dl 72 h after injection. These findings have far-reaching implications related to the current clinical practice in Italy of prophylaxis with intramuscular vitamin E, using the scantily bioavailable olive oil formulation currently on the market.
维生素E（α-生育酚）在新生儿重症监护病房中被广泛使用，其剂量、用药方案及剂型各不相同，用于预防早产儿脑室内出血、晶状体后纤维增生症、支气管肺发育不良和溶血性贫血。作为评估维生素E作用的一个更广泛项目的一部分，本研究旨在确定目前在意大利和其他欧洲国家唯一可用的肌肉注射剂型（橄榄油溶液），并按照标准方案在所有意大利新生儿重症监护病房中广泛使用，与在英国和加拿大临床试验中使用的胶体水溶液相比，是否能达到并维持建议的治疗水平。英国和加拿大的胶体水溶液含有α-生育酚醋酸酯，美国使用的含有游离生育酚，但在意大利尚未上市。44名孕周小于32周、出生体重670 - 1800克的婴儿被随机分配到两种剂型中的一种。我们在出生后8小时内（第0天）开始，连续3天每天肌肉注射20毫克/千克维生素E，24小时和48小时后（第1天和第2天）再次注射。在出生后第六天之前采集血液、血浆、输血后的红细胞和乳汁样本。收集直至新生儿重症监护病房出院时的临床数据。胶体水溶液注射后24小时血浆维生素E（游离生育酚）浓度平均为1.1，72小时时为3.3毫克/分升，而橄榄油溶液注射后浓度约低6倍。注射橄榄油制剂后血浆维生素E水平未超过基线。仅在使用胶体水溶液制剂后测量了维生素E醋酸酯，注射后72小时血浆最高浓度平均为1.01毫克/分升。这些发现对意大利目前使用市场上生物利用度低的橄榄油制剂进行肌肉注射维生素E预防的临床实践具有深远影响。
