Interactions Between Pomegranate Juice and CYP3A

描述(申请人提供)：近年来，石榴汁的消费量有所增加，因为人们发现了它对健康的诸多好处。然而，在人体微粒体和大鼠身上的实验表明，石榴汁可以显著抑制细胞色素P4503A(CyP3A)的活性。本应用的第一个目的是研究石榴汁与人微粒体和新鲜肝细胞中的细胞色素P3A的相互作用。这些研究将确定石榴汁在多大程度上抑制或诱导细胞色素P3A，以及石榴汁中的哪些成分对观察到的效果负责。这种相互作用的临床相关性将在受控的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，可以模拟这种相互作用的药代动力学。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，这种相互作用的药效学将通过监测在没有和存在石榴汁的情况下的镇静和精神运动表现来研究。

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.