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.

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。成人艾滋病临床试验5043组检测了在血清阴性个体中，加入奈非那韦、因地那韦、利托那韦或沙奎那韦前后，安非那韦（APV）和依非韦伦（EFV）以及加入奈非那韦（NFV）、因地那韦（IDV）、利托那韦（RTV）或沙奎那韦（SQV）时的药代动力学（PK）相互作用。单剂量APV给药后（第0天）进行PK研究。受试者（n=56）每24小时服用600 mg，持续10天，第11至13天用EFV重新启动APV，第14天进行PK研究。第15天，在APV和EFV中加入第二种蛋白酶抑制剂（PI） （NFV, 1250 mg, q12h； IDV, 1200 mg, q12h； RTV, 100mg, q12h；或SQV， 1600 mg, q12h），第21天进行PK研究。继续控制APV和EFV，不需要第二个PI。采用Wilcoxon符号秩检验比较受试者第0、14、21天的APV曲线下面积（auc）。计算几何平均比（GMR）周围的90%置信区间。EFV组APV AUC降低46% ~ 61% （AUC中位数百分比）（第14天与第0天相比，P值<0.05）。在NFV、IDV和RTV组中，合并EFV的第21天APV auc高于单独EFV的auc。NFV的GMR 90%置信区间为3.5 ~ 5.3 (P<0.001)， IDV为2.8 ~ 4.5 (P<0.001)， RTV为7.8 ~ 11.5 （P = 0.004）。沙奎那韦适度增加APV aus （GMR, 0.7 ~ 1.0; P = 0.042）。非西班牙裔美国人服用依非韦伦第14天的auc高于非西班牙裔白人。我们得出结论，EFV降低了APV auc，但奈非那韦、茚那韦或利托那韦补偿了EFV诱导。