Effect of food on the pharmacokinetics of erlotinib, an orally active epidermal growth factor receptor tyrosine-kinase inhibitor, in healthy individuals
Effect of food on the pharmacokinetics of erlotinib, an orally active epidermal growth factor receptor tyrosine-kinase inhibitor, in healthy individuals
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DOI：
10.1097/cad.0b013e3282f2d8e4
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发表时间：
2008-02-01
影响因子：
2.3
通讯作者：
Rakhit, Ashok
中科院分区：
文献类型：
--
作者：
Ling, Jie;Fettner, Scott;Rakhit, Ashok
在两项开放标签、随机研究中研究了食物对厄洛替尼药代动力学的影响。在一项单次给药交叉研究（n = 18）中，在空腹或进食条件下给予150 mg厄洛替尼。在第一阶段，餐后条件下观察到的几何平均值比（GMR）为2.09，证明血浆浓度-时间曲线下面积约加倍;而在第二阶段，GMR为0.93，出现下降。在一项多剂量平行研究（n=22）中，每天给予100 mg厄洛替尼，持续8天，禁食7天，然后在第8天进食，或相反顺序。在本研究中，食物导致第1天血浆浓度-时间曲线增加，GMR为1.66（P=0.015）。相比之下，第7天仅增加37%，GMR为1.34（P=0.252）。这些研究表明，食物可显著增加厄洛替尼的血浆暴露量。鉴于临床实践中使用的厄洛替尼的最大耐受剂量，我们建议在空腹条件下服用厄洛替尼。
The effects of food on the pharmacokinetics of erlotinib were investigated in two open-label, randomized studies. In a single-dose crossover study (n = 18), 150 mg of erlotinib was administered under either fasting or fed conditions. In the first period, an approximate doubling in the area under the plasma concentration-time curve was evidenced by the geometric mean ratio (GMR) of 2.09 observed under fed conditions; whereas, in the second period there was a decrease, with a GMR of 0.93. In a multiple-dose parallel study (n=22), 100 mg of erlotinib was administered daily for 8 days, either 7 days of fasting followed by feeding on day 8, or the reverse sequence. In this study, food resulted in an increase in the plasma concentration-time curve on day 1, with a GMR of 1.66 (P=0.015). In contrast, there was only a 37% increase on day 7, with a GMR of 1.34 (P=0.252). These studies indicate that food can substantially increase plasma exposure to erlotinib. Given the maximum tolerated dose of erlotinib used in clinical practice, we recommend that erlotinib be taken under conditions of fasting.