Clinical Pharmacology, Oncology Business Unit, Pfizer Inc., 10555 Science Center Drive, San Diego, CA 92121, USA.
Cancer Chemother Pharmacol. 2012 Jul;70(1):103-12. doi: 10.1007/s00280-012-1888-9. Epub 2012 May 27.
To evaluate the effect of food on axitinib pharmacokinetics in healthy volunteers with two different crystal polymorphs.
Two separate open-label, randomized, single-dose, three-period, crossover trials were conducted. Study I, conducted first using 5-mg axitinib Form IV film-coated immediate-release (FCIR) tablets, enrolled 18 subjects to compare fed versus fasted states and 24 subjects to evaluate the effect of timing of food consumption on axitinib pharmacokinetics. Study II enrolled 30 subjects to assess the effect of food using 5-mg axitinib Form XLI FCIR tablets. Subjects received axitinib after overnight fasting, with limited fasting or, depending on the study design, after consuming high-fat, high-calorie or moderate-fat, standard-calorie meals.
For Form IV FCIR, compared with overnight fasting, axitinib plasma exposure [area under the concentration curve (AUC)] was decreased 23 % when administered with food. For Form XLI FCIR, mean axitinib plasma AUC and maximum plasma concentration (C(max)) were 19 and 11 % higher, respectively, with a high-fat, high-calorie meal compared with overnight fasting. When Form XLI FCIR was administered with moderate-fat, standard-calorie meal, AUC and C(max) were 10 and 16 % lower compared with overnight fasting. Both formulations were well tolerated. Adverse events, mostly gastrointestinal (7 % with Form IV FCIR and 13 % with Form XLI FCIR), were mild to moderate in both studies.
While axitinib Form IV FCIR was associated with higher plasma exposure after overnight fasting, axitinib Form XLI FCIR can be administered with or without food as differences in axitinib pharmacokinetics under the two conditions were not clinically meaningful.
评估两种不同晶型的阿昔替尼在健康志愿者中的食物对药代动力学的影响。
进行了两项单独的、开放标签、随机、单剂量、三周期、交叉试验。研究 I 首先使用 5 毫克阿昔替尼晶型 IV 薄膜包衣速释（FCIR）片剂进行，共纳入 18 名受试者，比较禁食和进食状态，并纳入 24 名受试者评估进食时间对阿昔替尼药代动力学的影响。研究 II 纳入 30 名受试者，使用 5 毫克阿昔替尼晶型 XLI FCIR 片剂评估食物的影响。受试者在禁食过夜后、限制禁食或根据研究设计在进食高脂肪、高热量或中脂肪、标准热量餐 1 小时后接受阿昔替尼治疗。
对于晶型 IV FCIR，与禁食过夜相比，进食时阿昔替尼的血浆暴露（浓度-时间曲线下面积，AUC）降低了 23%。对于晶型 XLI FCIR，高脂肪、高热量餐与禁食过夜相比，阿昔替尼的平均血浆 AUC 和最大血浆浓度（C(max)）分别升高了 19%和 11%。当给予中脂肪、标准热量餐时，与禁食过夜相比，AUC 和 C(max)分别降低了 10%和 16%。两种制剂均耐受良好。不良事件主要为胃肠道（晶型 IV FCIR 为 7%，晶型 XLI FCIR 为 13%），在两项研究中均为轻度至中度。
虽然晶型 IV FCIR 与禁食过夜后更高的血浆暴露相关，但晶型 XLI FCIR 可在进食或不进食时给予，因为两种条件下阿昔替尼药代动力学的差异无临床意义。
