Shiomi Mari, Matsuki Shunji, Ikeda Atsushi, Ishikawa Tomohiro, Nishino Noriaki, Kimura Miyuki, Irie Shin
Clinical Development Department, Pharmaceutical Division, Japan Tobacco Inc., Tokyo, Japan.
J Clin Pharmacol. 2014 Jun;54(6):640-8. doi: 10.1002/jcph.283. Epub 2014 Mar 18.
This study investigated the effects of ingested food types on the pharmacokinetics of elvitegravir, cobicistat, emtricitabine, and tenofovir as a single-tablet regimen (STR) in Japanese HIV-negative healthy subjects. In this open-label, randomized, three-way crossover study, the pharmacokinetic profiles of elvitegravir, cobicistat, emtricitabine, and tenofovir were evaluated when administered with a standard breakfast, under fasting conditions, or with a nutritional protein-rich drink. All subjects (N = 11) received a single morning dose of elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (150/150/200/300 mg). Administration under fasting conditions resulted in decreases in the mean AUCinf of elvitegravir and tenofovir by 50% and 28%, respectively, relative to administration with a standard breakfast, whereas the bioavailabilities of elvitegravir and tenofovir were comparable when administered with a standard breakfast or a nutritional protein-rich drink. Under fasting conditions, it appears that the bioavailabilities of elvitegravir and tenofovir were not equivalent to those when they were administered with either type of food, although they were bioequivalent to each other under fed conditions. Cobicistat and emtricitabine were bioequivalent under all conditions. These findings suggest that elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate should be administered with food, and that the bioavailability of elvitegravir and tenofovir is not affected by the type of meal ingested.
本研究调查了摄入的食物类型对日本HIV阴性健康受试者中作为单片复方制剂(STR)的埃替格韦、考比司他、恩曲他滨和替诺福韦药代动力学的影响。在这项开放标签、随机、三交叉研究中,评估了埃替格韦、考比司他、恩曲他滨和替诺福韦在与标准早餐一起服用、空腹条件下或与富含营养蛋白质的饮料一起服用时的药代动力学特征。所有受试者(N = 11)均在早晨单次服用埃替格韦/考比司他/恩曲他滨/富马酸替诺福韦二吡呋酯(150/150/200/300 mg)。与标准早餐一起服用相比,空腹条件下给药导致埃替格韦和替诺福韦的平均AUCinf分别降低了50%和28%,而与标准早餐或富含营养蛋白质的饮料一起服用时,埃替格韦和替诺福韦的生物利用度相当。在空腹条件下,埃替格韦和替诺福韦的生物利用度似乎与它们与任何一种食物一起服用时的生物利用度不等效,尽管它们在进食条件下彼此生物等效。考比司他和恩曲他滨在所有条件下均生物等效。这些发现表明,埃替格韦/考比司他/恩曲他滨/富马酸替诺福韦二吡呋酯应与食物一起服用,并且埃替格韦和替诺福韦的生物利用度不受摄入食物类型的影响。