PHARMACOKINETIC INTERACTION BETWEEN EFAVIRENZ AND DUAL PROTEASE INHIBITORS

依非韦伦和双蛋白酶抑制剂之间的药代动力学相互作用

• 批准号: 8168755
• 负责人: Qing Ma
• 金额: $ 1.23万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-03-10 至 2010-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8168755
• 关键词: AIDS clinical trial group; Amprenavir; Cell Respiration; Complex; Computer Retrieval of Information on Scientific Projects Database; Dose; Drug Kinetics; Funding; Grant; HIV-1 protease; Indinavir; Institution; Linear Regressions; Modeling; Nelfinavir; Plasma; Protease Inhibitor; Randomized; Research; Research Personnel; Resources; Ritonavir; Saquinavir; Secondary to; Source; United States National Institutes of Health; Weight; efavirenz; healthy volunteer; open label; prospective

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. The combination of efavirenz with HIV-1 protease inhibitors (PI) results in complex interactions secondary to mixed induction and inhibition of oxidative metabolism. ACTG A5043 was a prospective, open-label, controlled, two-period, multiple-dose study with 55 healthy volunteers. The objective of the present study was to evaluate the potential pharmacokinetic interaction between efavirenz and dual PIs. The subjects received a daily dose of 600 mg efavirenz for 10 days with amprenavir 600 mg twice daily added at day 11 and were randomized to receive nelfinavir, indinavir, ritonavir, saquinavir, or no second PI on days 15-21. Intensive pharmacokinetic studies were conducted on day 14 and 21. Efavirenz plasma concentrations were fit to candidate models using weighted non-linear regression.

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。 依法韦仑与HIV-1蛋白酶抑制剂（PI）的组合导致继发于氧化代谢的混合诱导和抑制的复杂相互作用。ACTG A5043是一项在55名健康志愿者中进行的前瞻性、开放标签、对照、两阶段、多次给药研究。本研究的目的是评价依非韦伦和双重PI之间的潜在药代动力学相互作用。受试者接受依非韦伦600 mg每日剂量，持续10天，第11天添加安普那韦600 mg每日两次，第15-21天随机接受奈非那韦、茚地那韦、利托那韦、沙奎那韦或不接受第二次PI。在第14天和第21天进行了密集的药代动力学研究。使用加权非线性回归将依法韦仑血浆浓度拟合至候选模型。