COMPARISON OF CYTOCHROME P4503A4 ACTIVITY IN FED AND FASTING HEALTHY SUBJECTS

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。使用动物和体外模型，我们最近发现，禁食导致诱导CYP 3A 4（肝细胞色素P450酶的成员）的活性。我们的数据进一步表明，这种活动可能发生在人类身上。鉴于给药相对于进食时间的广泛变异性，我们的临床前数据表明，禁食/进食与CYP 3A 4活性之间的关系可能对给药以及控制许多药物的治疗和毒性作用具有广泛意义。我们建议通过一种经过测试和验证的测定方法，红霉素呼气试验（ERBMT），研究正常志愿者进食和空腹时CYP 3A 4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).