Amprenavir and efavirenz pharmacokinetics before and after the addition of nelfinavir, indinavir, ritonavir, or saquinavir in seronegative individuals
Amprenavir and efavirenz pharmacokinetics before and after the addition of nelfinavir, indinavir, ritonavir, or saquinavir in seronegative individuals
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DOI：
10.1128/aac.49.8.3373-3381.2005
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发表时间：
2005-08-01
影响因子：
4.9
通讯作者：
Reichman, RC
中科院分区：
文献类型：
--
作者：
Morse, GD;Rosenkranz, S;Reichman, RC
成人艾滋病临床试验组5043检测了安非那韦（APV）和依非韦伦（EFY）单独使用以及加入奈非那韦（NFV）、茚地那韦（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（每24小时）接受600 mg EFV，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, 1,250 mg, q12h； IDV, 1,200 mg, q12h； RTV, 100 mg, q12h；或SQV， 1,600 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 auc （GMR, 1.0 ~ 1.4; P 0.106）。对照组第21天auc低于第14天（GMR, 0.7 ~ 1.0; P 0.042）。非西班牙裔美国人第14天服用依非韦伦的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。
Adult AIDS Clinical Trials Group 5043 examined pharmacokinetic (PK) interactions between amprenavir (APV) and efavirenz (EFY) 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.