AMPRENAVIR AND EFAVIRENZ PHARMACOKINETICS BEFORE AND AFTER THE ADDITION OF

安普那韦和依非韦伦添加前后的药代动力学

• 批准号: 7355259
• 负责人: Gene D. Morse
• 金额: $ 1.39万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-02-01 至 2007-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7355259
• 关键词: AMPRENAVIR; EFAVIRENZ; PHARMACOKINETICS; BEFORE; AFTER

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. Amprenavir and Efavirenz Pharmacokinetics before and after the addition of Nelfinavir, Indinavir, Ritonavir, or Saquinavir in Seronegative Individuals: Adult AIDS Clinical Trials Group 5043 examined pharmacokinetic (PK) interactions between amprenavir (APV) and efavirenz (EFV) both by themselves and when nelfinavir (NFV), indinavir (IDV), ritonavir (RTV), or saquinavir (SQV) is added. A PK study was conducted after the administration of single doses of APV (day 0). Subjects (n=56) received 600 mg every 24 h (q24h) for 10 days and restarted APV with EFV for days 11 to 13 with a PK study on day 14. A second protease inhibitor (PI) (NFV, 1250 mg, q12h; IDV, 1,200 mg, q12h; RTV 100mg, q12h; or SQV, 1600 mg, q12h) was added to APV and EFV on day 15, and a PK study was conducted on day 21. Controls continued APV and EFV without a second PI. Among subjects, the APV areas under the curve (AUCs) on days 0, 14, and 21 were compared using the Wilcoxon signed-rank test. Ninety-percent confidence intervals around the geometric mean ratios (GMR) were calculated. APV AUCs were 46% to 61% lower (median percentage of AUC) with EFV (day 14 versus day 0; P values of <0.05). In the NFV, IDV, and RTV groups, day 21 APV AUCs with EFV were higher than AUCs for EFV alone. Ninety-percent confidence intervals around the GMR were 3.5 to 5.3 for NFV (P<0.001), 2.8 to 4.5 for IDV (P < 0.001), and 7.8 to 11.5 for RTV (P = 0.004). Saquinavir modestly increased the APV AUCs (GMR, 0.7 to 1.0; P = 0.042). African-American non-Hispanics had higher day 14 efavirenz AUCs that white non-Hispanics. We conclude that EFV lowered APV AUCs, but nelfinavir, indinavir, or ritonavir compensated for EFV induction.

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子弹和调查员（PI）可能已经从其他NIH来源获得了主要资金，因此可以在其他清晰的条目中代表。列出的机构适用于该中心，这不一定是调查员的机构。在血清负格的个体中添加Nelfinavir，Indinavir，Ritonavir或Saquinavir之前和之后的Amprenavir和Efavirenz药代动力学。添加了Indinavir（IDV），Ritonavir（RTV）或Saquinavir（SQV）。单剂量的APV（第0天）进行了PK研究。 Subjects (n=56) received 600 mg every 24 h (q24h) for 10 days and restarted APV with EFV for days 11 to 13 with a PK study on day 14. A second protease inhibitor (PI) (NFV, 1250 mg, q12h; I​​DV, 1,200 mg, q12h; RTV 100mg, q12h; or SQV, 1600 mg, q12h) was在第15天添加到APV和EFV中，并在第21天进行了PK研究。对照持续的APV和EFV没有第二个PI。在受试者中，使用Wilcoxon签名的测试比较了第0、14和21天的曲线下的APV区域（AUC）。计算了几何平均比率（GMR）周围的91％置信区间。 APV AUC的AUC为EFV的46％至61％（AUC的中位百分比）（第14天对第0天； P值<0.05）。在NFV，IDV和RTV组中，仅EFV的EFV的第21天APV AUC高于AUC。对于NFV，GMR周围的91％置信区间为3.5至5.3（P <0.001），IDV为2.8至4.5（P <0.001），RTV为7.8至11.5（P = 0.004）。 Saquinavir适度增加了APV AUC（GMR，0.7至1.0； P = 0.042）。非裔美国人的非西班牙裔人在14年的Efavirenz Aucs中有较高的白色非西班牙裔。我们得出的结论是，EFV降低了APV AUC，但是Nelfinavir，Indinavir或Ritonavir赔偿了EFV诱导。