INDUCTIVE EFFECTS OF NELFINAVIR AND RITONAVIR

奈非那韦和利托那韦的诱导作用

• 批准号: 7603474
• 负责人: Ann Cornwall Collier
• 金额: $ 2.11万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-04-01 至 2007-09-16
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7603474
• 关键词: Computer Retrieval of Information on Scientific Projects Database; Cytochrome P450; Drug Interactions; Enzymes; Funding; Grant; HIV Protease Inhibitors; In Vitro; Institution; Measures; Nelfinavir; P-Glycoprotein; P-Glycoproteins; Pharmaceutical Preparations; Protease Inhibitor; Research; Research Personnel; Resources; Rifampin; Ritonavir; Source; United States National Institutes of Health; clinically relevant; enzyme activity; in vivo

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.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 利托那韦和奈非那韦等抗 HIV 蛋白酶抑制剂 (PI) 容易产生临床相关的诱导性和抑制性药物相互作用。 为了量化 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：1A2、2C9、2D6、3A 和 P-糖蛋白 (P-gp)。 我们将通过在奈非那韦或利托那韦诱导之前和之后施用药物来测量这些酶和转运蛋白的体内活性来实现这一目标。 为了帮助将这些结果与体外获得的结果关联起来，我们将比较 PI 对 CYP 和 P-gp 的体内诱导与用利福平（一种众所周知的 CYP 酶和 P-gp 诱导剂）获得的体内诱导。