PHARMACOKINETIC INTERACTION BETWEEN EFAVIRENZ AND DUAL PROTEASE INHIBITORS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 Eefavirenz与HIV-1蛋白酶抑制剂(PI)的结合导致复杂的相互作用，继而导致氧化代谢的混合诱导和抑制。ACTG A5043是一项前瞻性、开放标签、对照、两个周期、多次给药的研究，有55名健康志愿者参加。本研究的目的是评估Eefavirenz和双PI之间潜在的药代动力学相互作用。受试者在第11天接受每日600毫克的依法韦仑治疗，并在第11天加入氨丙那韦600毫克，每天两次，并在第15-21天随机接受奈非那韦、依地那韦、利托那韦、沙奎那韦或不接受第二次静脉注射。在第14天和第21天进行了密集的药代动力学研究。经加权非线性回归分析，依法韦仑血药浓度符合候选模型。

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.