INDUCTIVE EFFECTS OF NELFINAVIR AND RITONAVIR

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。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 研究中心，而研究中心不一定是研究者所在的机构。 抗HIV蛋白酶抑制剂（PI）如利托那韦和奈非那韦倾向于产生临床相关的诱导和抑制药物相互作用。 为了定量PI的诱导药物相互作用，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）活性的程度：1A 2、2C 9、2D 6、3A和P-糖蛋白（P-gp）。 我们将通过给药药物来实现这一点，这些药物将测量这些酶和转运蛋白在奈非那韦或利托那韦诱导前后的体内活性。 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PI对CYP和P-gp的体内诱导与利福平（一种众所周知的CYP酶和P-gp诱导剂）的体内诱导。

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 (PIs) like ritonavir and nelfinavir have the propensity to produce clinically-relevant inductive and inhibitory drug interactions. To quantify inductive drug interactions of the PIs, 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 PIs to that obtained with rifampin, a well known inducer of CYP enzymes and P-gp.