Lack of a Significant Drug Interaction between Raltegravir and Tenofovir
Lack of a Significant Drug Interaction between Raltegravir and Tenofovir
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DOI：
10.1128/aac.00005-08
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发表时间：
2008-07
影响因子：
4.9
通讯作者：
L. Wenning;E. Friedman;J. Kost;S. Breidinger;J. Stek;K. Lasseter;K. Gottesdiener;Joshua Chen;H. Teppler;J. Wagner;J. Stone;Marian Iwamoto
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文献类型：
--
作者：
L. Wenning;E. Friedman;J. Kost;S. Breidinger;J. Stek;K. Lasseter;K. Gottesdiener;Joshua Chen;H. Teppler;J. Wagner;J. Stone;Marian Iwamoto
摘要雷特格韦是一种新型的人类免疫缺陷病毒1型（HIV-1）整合酶抑制剂，具有较强的体外活性（在50%人血清中的95%抑制浓度为31 nM）。本文报告了一项在健康受试者中进行的开放标签、序贯、三阶段研究的结果。第1阶段为雷特格韦400 mg，每日2次，持续4天;第2阶段为富马酸替诺福韦二异丙酯（TDF）300 mg，每日1次，持续7天;第3阶段为雷特格韦400 mg，每日2次+TDF 300 mg，每日1次，持续4天。还在HIV-1感染患者中测定了雷特格韦单药治疗与雷特格韦联合TDF和拉米夫定治疗的药代动力学特征。TDF对雷特格韦无临床显著影响。在健康受试者中，0 - 12 h的雷特格韦浓度-时间曲线下面积（AUC0 - 12）和血浆药物峰浓度（Cmax）适度增加（几何均值比[GMR]分别为1.49和1.64）。在健康受试者中，TDF对给药后12小时（C12）的雷特格韦浓度没有实质性影响（GMR [TDF+雷特格韦-雷特格韦单药]，1.03; 90%置信区间[CI]，0.73 - 1.45），而在HIV-1感染患者中观察到适度增加（GMR，1.42; 90% CI，0.89 - 2.28）。雷特格韦对替诺福韦的药代动力学没有实质性影响：C24、AUC和Cmax GMR分别为0.87、0.90和0.77。雷特格韦和TDF联合给药不会使任一药物的药代动力学发生具有临床意义的改变。雷特格韦和TDF可同时给药，无需调整剂量。
ABSTRACT Raltegravir is a novel human immunodeficiency virus type 1 (HIV-1) integrase inhibitor with potent in vitro activity (95% inhibitory concentration of 31 nM in 50% human serum). This article reports the results of an open-label, sequential, three-period study of healthy subjects. Period 1 involved raltegravir at 400 mg twice daily for 4 days, period 2 involved tenofovir disoproxil fumarate (TDF) at 300 mg once daily for 7 days, and period 3 involved raltegravir at 400 mg twice daily plus TDF at 300 mg once daily for 4 days. Pharmacokinetic profiles were also determined in HIV-1-infected patients dosed with raltegravir monotherapy versus raltegravir in combination with TDF and lamivudine. There was no clinically significant effect of TDF on raltegravir. The raltegravir area under the concentration time curve from 0 to 12 h (AUC0-12) and peak plasma drug concentration (Cmax) were modestly increased in healthy subjects (geometric mean ratios [GMRs], 1.49 and 1.64, respectively). There was no substantial effect of TDF on raltegravir concentration at 12 h postdose (C12) in healthy subjects (GMR [TDF plus raltegravir-raltegravir alone], 1.03; 90% confidence interval [CI], 0.73 to 1.45), while a modest increase (GMR, 1.42; 90% CI, 0.89 to 2.28) was seen in HIV-1-infected patients. Raltegravir had no substantial effect on tenofovir pharmacokinetics: C24, AUC, and Cmax GMRs were 0.87, 0.90, and 0.77, respectively. Coadministration of raltegravir and TDF does not change the pharmacokinetics of either drug to a clinically meaningful degree. Raltegravir and TDF may be coadministered without dose adjustments.