Chanel Hsiang, Faisal Shakeel, Nicholas Farina, Ken Johnson, Daniel L Hertz
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引用次数: 0
Abstract
Propofol is commonly used to sedate patients, but variations in how individuals metabolize the drug may affect dosing requirements. The objective of this study was to explore how genetic variations in CYP450 enzymes, particularly CYP2B6, influence propofol metabolism in ICU patients receiving mechanical ventilation. Genetic variants of CYP2B6, CYP2C9, CYP2C19, and CYP3A5 were collected from an institutional genetic data repository. Patients were dichotomized into low and high metabolic activity for each enzyme, and the mean weight- and time-normalized propofol dose administered was compared between groups via t test. There was no significant difference in average daily propofol dose between patients with low and high CYP2B6 activity (11 vs. 11 mg/kg/h, P = 0.78), or any of the other CYP enzymes analyzed (all P > 0.05). This study could not replicate previous studies indicating that patients carrying genetic variants with diminished CYP2B6 activity required lower propofol doses. Future studies with prospectively collected dosing and outcomes data, and measurement of plasma drug concentrations, may provide insights into personalized propofol dosing strategies.
异丙酚通常用于镇静患者,但个体代谢药物的差异可能会影响剂量要求。本研究的目的是探讨CYP450酶,特别是CYP2B6的遗传变异如何影响ICU机械通气患者异丙酚代谢。CYP2B6、CYP2C9、CYP2C19和CYP3A5的遗传变异从机构遗传数据库中收集。将患者分为每种酶的低代谢活性和高代谢活性,并通过t检验比较各组之间的平均体重和时间标准化异丙酚剂量。CYP2B6活性低和高的患者的平均每日异丙酚剂量(11 mg/kg/h vs 11 mg/kg/h, P = 0.78)或任何其他CYP酶分析(P均为0.05)无显著差异。这项研究不能重复先前的研究,表明携带CYP2B6活性降低的基因变异的患者需要更低的异丙酚剂量。未来的前瞻性研究收集剂量和结局数据,以及血浆药物浓度的测量,可能会为个性化异丙酚剂量策略提供见解。
期刊介绍:
Pharmacogenetics and Genomics is devoted to the rapid publication of research papers, brief review articles and short communications on genetic determinants in response to drugs and other chemicals in humans and animals. The Journal brings together papers from the entire spectrum of biomedical research and science, including biochemistry, bioinformatics, clinical pharmacology, clinical pharmacy, epidemiology, genetics, genomics, molecular biology, pharmacology, pharmaceutical sciences, and toxicology. Under a single cover, the Journal provides a forum for all aspects of the genetics and genomics of host response to exogenous chemicals: from the gene to the clinic.