Katsuya Yuki, Fujiwara Yutaka, Sunami Kuniko, Utsumi Hirofumi, Goto Yasushi, Kanda Shintaro, Horinouchi Hidehito, Nokihara Hiroshi, Yamamoto Noboru, Takashima Yuki, Osawa Satoko, Ohe Yuichiro, Tamura Tomohide, Hamada Akinobu
Department of Thoracic Oncology, National Cancer Center Hospital, Tsukiji 5-1-1, Chuo-ku, Tokyo, 104-0045, Japan,
Cancer Chemother Pharmacol. 2015 Jul;76(1):125-32. doi: 10.1007/s00280-015-2778-8. Epub 2015 May 21.
The recommended dose of erlotinib is 150 mg daily either 1 h before a meal (complete fasting) or 2 h after a meal (2 h post-meal), because of the food effect.
We conducted a cross-over pharmacokinetic study to compare the fed bioequivalence in the two conditions.
Twenty-three patients with non-small cell lung cancer were included in the analysis. AUC0-24 and C max in the 2-h post-meal status were significantly higher than in the complete fasting status (GMR = 1.33, P < 0.001; GMR = 1.44, P < 0.001, respectively). However, because the concentration of erlotinib did not reach the steady state within 7 days in the complete fasting state, we conducted analyses only on day 14, which showed no significant difference in AUC0-24 or C max between the two conditions. The more rapid increase in AUC0-24 and C min did not produce any earlier and more severe toxic events.
The AUC0-24 increased significantly faster (48-53 % greater) in the 2-h post-meal status than in complete fasting status, which suggested that the two gastric emptying states might differ in their absorption. However, there was no clinically significant difference in bioavailability or toxicity between the two clinically used fed conditions at least in 14 days.
由于食物的影响，厄洛替尼的推荐剂量为每日150毫克，可在饭前1小时（完全空腹）或饭后2小时服用。
我们进行了一项交叉药代动力学研究，以比较这两种情况下的进食生物等效性。
23例非小细胞肺癌患者纳入分析。饭后2小时状态下的AUC0-24和Cmax显著高于完全空腹状态（几何平均比值分别为1.33，P<0.001；1.44，P<0.001）。然而，由于完全空腹状态下厄洛替尼的浓度在7天内未达到稳态，我们仅在第14天进行分析，结果显示两种状态下的AUC0-24或Cmax无显著差异。AUC0-24和Cmin的更快升高并未导致任何更早、更严重的毒性事件。
饭后2小时状态下的AUC0-24升高速度明显更快（比完全空腹状态高48%-53%），这表明两种胃排空状态的吸收情况可能不同。然而，至少在14天内，两种临床使用的进食状态下的生物利用度或毒性在临床上无显著差异。
