Interactions Between Pomegranate Juice and CYP3A

石榴汁和 CYP3A 之间的相互作用

• 批准号: 7112596
• 负责人: Dora Farkas
• 金额: $ 4.88万
• 依托单位: TUFTS UNIVERSITY BOSTON
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-07 至 2008-09-06
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7112596
• 关键词: clinical research; clinical trials; cytochrome P450; human; liver cells; microsomes; pharmacokinetics

DESCRIPTION (provided by applicant): The consumption of pomegranate juice has increased in recent years after the discovery of its numerous health benefits. However, experiments in human microsomes and rats have demonstrated that pomegranate juice can significantly inhibit the activity of cytochrome P450 3A (CYP3A). The first aim of this application is to study the interaction between pomegranate juice and CYP3A in human microsomes and fresh hepatocytes. These studies will determine to what extent pomegranate juice inhibits or induces CYP3A and which components in the juice are responsible for the observed effect. The clinical relevance of this interaction will be investigated in controlled pharmacokinetic and pharmacodynamic studies.Triazolam is a safe clinical probe and by monitoring the formation of its metabolites the pharmacokinetics of this interaction can be modeled. Since triazolam is a sedative, inhibition of CYP3A activity could influence its effect on the central nervous system. Thus, the pharmacodynamics of this interaction will be studied by monitoring sedation and psychomotor performance in the absence and presence of pomegranate juice.

描述（由申请人提供）：近年来，在发现石榴汁的众多健康益处后，石榴汁的消费量有所增加。然而，人体微粒体和大鼠实验表明，石榴汁可以显着抑制细胞色素P450 3A（CYP3A）的活性。该应用的首要目的是研究石榴汁与人微粒体和新鲜肝细胞中 CYP3A 之间的相互作用。这些研究将确定石榴汁抑制或诱导 CYP3A 的程度，以及石榴汁中的哪些成分导致了观察到的效果。这种相互作用的临床相关性将在受控药代动力学和药效学研究中进行研究。三唑仑是一种安全的临床探针，通过监测其代谢物的形成，可以对这种相互作用的药代动力学进行建模。由于三唑仑是一种镇静剂，抑制 CYP3A 活性可能会影响其对中枢神经系统的作用。因此，将通过监测石榴汁不存在和存在下的镇静和精神运动表现来研究这种相互作用的药效学。