Ramanathan Srinivasan, Cheng Andrew, Mittan Angelique, Ebrahimi Ramin, Kearney Brian P
Gilead Sciences Inc, Foster City, CA 94404, USA.
J Clin Pharmacol. 2006 May;46(5):559-66. doi: 10.1177/0091270006287704.
This was a 36-day, open-label, fixed-sequence, multiple-dose drug interaction study in 23 healthy subjects to evaluate the effects of multiple doses of tenofovir disoproxil fumarate on the single-dose pharmacokinetics of ribavirin. Subjects received a 600-mg once-daily oral dose of ribavirin on days 1 and 22 and 300-mg once-daily oral doses of tenofovir disoproxil fumarate on days 17 through 24. Pharmacokinetic sampling was performed on days 1 through 4 and 22 through 25. Pharmacokinetics of ribavirin was not altered by its coadministration with tenofovir disoproxil fumarate as the point estimates (day 22 [test treatment]/day 1 [reference treatment]), and the 90% confidence interval for maximum observed concentration (0.95; 88.7-101) and area under the plasma concentration-time curve up to time of last measurable concentration (1.12; 106-117) were within the equivalence bounds of 80% to 125%. Tenofovir pharmacokinetics after ribavirin coadministration was similar to that observed in previous studies. These results indicate that coadministration of tenofovir disoproxil fumarate and ribavirin does not result in substantial changes to their individual pharmacokinetic profiles.
这是一项为期36天的开放标签、固定序列、多剂量药物相互作用研究，在23名健康受试者中进行，以评估多剂量富马酸替诺福韦二吡呋酯对利巴韦林单剂量药代动力学的影响。受试者在第1天和第22天接受每日一次600毫克的口服利巴韦林剂量，并在第17天至第24天接受每日一次300毫克的口服富马酸替诺福韦二吡呋酯剂量。在第1天至第4天以及第22天至第25天进行药代动力学采样。利巴韦林与富马酸替诺福韦二吡呋酯合用时，其药代动力学未发生改变，作为点估计值（第22天[试验治疗]/第1天[对照治疗]），最大观察浓度的90%置信区间（0.95；88.7 - 101）以及直至最后可测量浓度时的血浆浓度-时间曲线下面积（1.12；106 - 117）均在80%至125%的等效范围内。利巴韦林合用时替诺福韦的药代动力学与先前研究中观察到的相似。这些结果表明，富马酸替诺福韦二吡呋酯和利巴韦林合用不会导致它们各自药代动力学特征发生实质性变化。
