Pharmacokinetics and metabolomics of vitamin D supplementation in critical illness

 描述（由申请人提供）：危重疾病是重大的公共卫生问题，因为其不良后果包括高死亡率和大量的医疗保健费用。危重病幸存者长期发病率和死亡率很高。生物学数据表明维生素D与危重患者的重要预后之间存在关系。最近发表的VITdAL-ICU试验是一项随机对照试验，表明在严重维生素D缺乏的重症患者中补充高剂量维生素D似乎可以改善死亡率。维生素D补充剂如何影响重症监护结果，以及哪些患者可能从维生素D补充剂中受益尚不清楚。我们建议使用来自已完成的VITdAL-ICU试验的人血液样本，通过检查高剂量维生素D补充剂的药代动力学和维生素D补充剂对循环代谢物的修饰，检查维生素D的保护机制，并确定生物学上合理的生物标志物。与危重病相关的发病率和死亡率仍然高得不可接受，迫切需要新的治疗方法来改善预后。维生素D是一种廉价的创新疗法，具有改善维生素D缺乏症重症患者预后的巨大潜力。

 DESCRIPTION (provided by applicant): Critical illnesses are significant public health issues because of adverse outcomes including the high mortality rate and substantial health care costs. Critical illness survivors suffer significant long-term morbidity and mortality. Biologic daa suggests a relationship between vitamin D and important outcomes in critically ill patients. The recently published VITdAL-ICU trial a randomized controlled trial demonstrates that high dose vitamin D supplementation in critically ill patients with severe vitamin D deficiency appears to improve mortality. How vitamin D supplementation impacts critical care outcomes and which patients may benefit from vitamin D supplementation is not clear. We propose to examine the mechanism of protection of vitamin D and identify biologically plausible biomarkers through examination of the pharmacokinetics of high dose vitamin D supplementation and the modification of circulating metabolites with vitamin D supplementation using human blood samples from the completed VITdAL-ICU trial. Morbidity and mortality related to critical illness remain unacceptably high and novel therapeutic approaches to improve outcomes are urgently needed. Vitamin D is an inexpensive and innovative therapy that has significant potential to improve outcomes in critically ill patients with vitamin D deficiency.