AMPRENAVIR AND EFAVIRENZ PHARMACOKINETICS BEFORE AND AFTER THE ADDITION OF

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。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。在血清阴性个体中添加奈非那韦、茚地那韦、利托那韦或沙奎那韦之前和之后的安普那韦和依法韦仑药代动力学：成人艾滋病临床试验组5043检查了安普那韦（APV）和依法韦仑（EFV）之间的药代动力学（PK）相互作用，包括单独使用以及添加奈非那韦（NFV）、茚地那韦（IDV）、利托那韦（RTV）或沙奎那韦（SQV）时。在APV单次给药后（第0天）进行PK研究。受试者（n=56）接受600 mg每24 h（q24 h）给药，持续10天，并在第11 - 13天使用EFV重新开始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，q12 h; IDV，1，200 mg，q12 h; RTV 100 mg，q12 h;或SQV，1600 mg，q12 h），并在第21天进行PK研究。对照组继续APV和EFV，无第二次PI。在受试者中，使用Wilcoxon符号秩检验比较第0、14和21天的APV曲线下面积（AUC）。计算几何均值比（GMR）的90%置信区间。EFV组的APV AUC降低46%至61%（AUC的中位数百分比）（第14天与第0天相比; P值<0.05）。在NFV、IDV和RTV组中，第21天APV AUC与EFV联合给药高于EFV单独给药的AUC。GMR的90%置信区间为NFV 3.5 ~ 5.3（P<0.001），IDV 2.8 ~ 4.5（P < 0.001），RTV 7.8 ~ 11.5（P = 0.004）。沙奎那韦适度增加APV AUC（GMR，0.7至1.0; P = 0.042）。非洲裔美国人非西班牙裔的第14天依非韦伦AUC高于非西班牙裔白色白人。我们的结论是，EFV降低APV AUC，但奈非那韦，茚地那韦，利托那韦补偿EFV诱导。

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.