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: 7954008
• 负责人: Qing Ma
• 金额: $ 0.65万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-02-01 至 2010-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7954008
• 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; Mass Spectrum Analysis; Modeling; Nelfinavir; Plasma; Protease Inhibitor; Randomized; Research; Research Personnel; Resources; Ritonavir; Saquinavir; Secondary to; Source; United States National Institutes of Health; Weight; biomedical resource; 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.

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。 依非韦伦与 HIV-1 蛋白酶抑制剂 (PI) 的组合会导致氧化代谢的混合诱导和抑制继发的复杂相互作用。 ACTG A5043 是一项前瞻性、开放标签、对照、两期、多剂量研究，有 55 名健康志愿者参与。本研究的目的是评估依非韦伦和双 PI 之间潜在的药代动力学相互作用。受试者每天服用 600 mg 依非韦伦，持续 10 天，并在第 11 天添加安普那韦 600 mg，每天两次，并在第 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 天进行了深入的药代动力学研究。使用加权非线性回归将依法韦仑血浆浓度拟合到候选模型。