INDUCTIVE EFFECTS OF NELFINAVIR AND RITONAVIR (I)

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。抗HIV蛋白水解酶抑制剂(PRI)如利托那韦和奈非那韦具有产生与临床相关的诱导性和抑制性药物相互作用的倾向。为了量化PRI的诱导性药物相互作用，我们希望确定奈非那韦或利托那韦诱导以下细胞色素P450酶(CYP)的活性的程度：1A2、2C9、2D6、3A和P-糖蛋白(P-gp)。我们将通过给药来测量奈非那韦或利托那韦诱导前后体内这些酶和转运蛋白的活性，从而实现这一点。为了帮助将这些结果与体外获得的结果相关联，我们将比较PRI和利福平对CyPS和P-gp的体内诱导作用，利福平是一种众所周知的CYP酶和P-gp的诱导剂。

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. Anti-HIV protease inhibitors (PRIs) like ritonavir and nelfinavir have the propensity to produce clinically-relevant inductive and inhibitory drug interactions. To quantify inductive drug interactions of the PRIs, we wish to determine the extent to which nelfinavir or ritonavir induce the activity of the following cytochrome P450 enzymes (CYP): 1A2, 2C9, 2D6, 3A and P-glycoprotein (P-gp). We will accomplish this by administering drugs which will measure the in vivo activities of these enzymes and transporter, both before and after induction with nelfinavir or ritonavir. To aid in correlating these results to results obtained in vitro we will compare the in vivo induction of CYPs and P-gp by the PRIs to that obtained with rifampin, a well known inducer of CYP enzymes and P-gp.