Morse Gene D, Rosenkranz Susan, Para Michael F, Segal Yoninah, Difrancesco Robin, Adams Elizabeth, Brizz Barbara, Yarasheski Kevin E, Reichman Richard C
Adult ACTG Pharmacology Support Laboratory, Pharmacotherapy Research Center, Department of Pharmacy Practice, School of Pharmacy and Pharmaceutical Sciences, 317 Hochstetter Hall, University at Buffalo, Amherst, NY 14260, USA.
Antimicrob Agents Chemother. 2005 Aug;49(8):3373-81. doi: 10.1128/AAC.49.8.3373-3381.2005.
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 of EFV 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, 1,250 mg, q12h; IDV, 1,200 mg, q12h; RTV, 100 mg, q12h; or SQV, 1,600 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, 1.0 to 1.4; P = 0.106). Control group AUCs were lower on day 21 compared to those on day 14 (GMR, 0.7 to 1.0; P = 0.042). African-American non-Hispanics had higher day 14 efavirenz AUCs than white non-Hispanics. We conclude that EFV lowered APV AUCs, but nelfinavir, indinavir, or ritonavir compensated for EFV induction.
成人艾滋病临床试验组5043研究了安普那韦（APV）与依非韦伦（EFV）单独使用时以及添加奈非那韦（NFV）、茚地那韦（IDV）、利托那韦（RTV）或沙奎那韦（SQV）后的药代动力学（PK）相互作用。在单次给予APV（第0天）后进行了一项PK研究。受试者（n = 56）每24小时（q24h）接受600毫克EFV，共10天，并在第11至13天重新开始使用APV与EFV联合用药，在第14天进行PK研究。在第15天，将第二种蛋白酶抑制剂（PI）（NFV，1250毫克，q12h；IDV，1200毫克，q12h；RTV，100毫克，q12h；或SQV，1600毫克，q12h）添加到APV和EFV中，并在第21天进行PK研究。对照组继续使用APV和EFV，不添加第二种PI。在受试者中，使用Wilcoxon符号秩检验比较第0天、第14天和第21天的APV曲线下面积（AUC）。计算几何平均比值（GMR）周围的90%置信区间。与EFV联合使用时（第14天与第0天相比；P值<0.05），APV的AUC降低了46%至61%（AUC的中位数百分比）。在NFV、IDV和RTV组中，第21天与EFV联合使用时的APV AUC高于单独使用EFV时的AUC。NFV的GMR周围90%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）。沙奎那韦适度增加了APV的AUC（GMR，1.0至1.4；P = 0.106）。与第14天相比，对照组在第21天的AUC较低（GMR，0.7至1.0；P = 0.042）。非西班牙裔非洲裔美国人在第14天的依非韦伦AUC高于非西班牙裔白人。我们得出结论，EFV降低了APV的AUC，但奈非那韦、茚地那韦或利托那韦可补偿EFV的诱导作用。
