COMPARISON OF CYTOCHROME P4503A4 ACTIVITY IN FED AND FASTING HEALTHY SUBJECTS

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。利用动物和体外模型，我们最近发现禁食可以诱导肝脏细胞色素P450酶的成员细胞色素3A4的活性。我们的数据进一步表明，这种活动很可能发生在人类身上。鉴于剂量随食物摄入时间的变化很大，我们的临床前数据表明，禁食/喂食和CYP3A4活性之间的关系可能对许多药物的剂量以及控制治疗和毒性作用具有广泛的意义。我们建议通过红霉素呼气试验(ERBMT)来研究喂食和禁食的正常志愿者中CYP3A4的活性。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Using animal and in vitro models, we recently found that fasting results in induction of activity of CYP3A4, member of the hepatic cytochrome P450 enzymes. Our data further suggest that this activity is likely to occur in humans. Given the wide variability in dosing relative to time of food intake, our preclinical data suggest that the relationship between fasting/feeding and CYP3A4 activity could have broad implications for dosing as well as control of therapeutic and toxic effects of numerous pharmacologic agents. We propose to study the activity of CYP3A4 in fed and fasting normal volunteers through a tested and validated assay, the erythromycin breath test (ERBMT).