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高昂的医疗费用。危重病幸存者长期存在严重的发病率和死亡率。生物学DAA提示维生素D与危重病患者的重要结局之间存在关系。最近发表的VITdAL-ICU试验是一项随机对照试验，表明在严重缺乏维生素D的危重患者中补充大剂量维生素D似乎可以提高死亡率。维生素D补充剂如何影响危重护理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。我们建议利用完成的VITdAL-ICU试验中的人体血液样本，通过检测大剂量维生素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，来研究维生素D的保护机制，并确定生物学上可信的生物标志物。与危重疾病相关的发病率和死亡率仍然高得令人无法接受，迫切需要新的治疗方法来改善结果。维生素D是一种廉价的创新疗法，具有显著改善维生素D缺乏症危重患者预后的潜力。

 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.