Interactions Between Pomegranate Juice and CYP3A

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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.