Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Clinical Pharmacology and Pharmacy, Cancer Centre Amsterdam, Amsterdam, The Netherlands.
Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam Public Health Research Institute, Amsterdam, The Netherlands.
Eur J Haematol. 2020 Aug;105(2):148-155. doi: 10.1111/ejh.13418. Epub 2020 Apr 16.
Taking advantage of its food-dependent bioavailability, the present study investigated the effect of a reduced dose taken with real-life meals on the pharmacokinetics (PK) of nilotinib in chronic myeloid leukaemia (CML) patients.
Nilotinib was taken fasted (300 mg BID, days 1-4) or with real-life meals (200 mg BID, days 5-11). Rich sampling (days 1, 3, 8, 11) allowed for non-compartmental PK analysis. Nilotinib exposure (AUC -C -C ) and its intra- and interpatient variability were compared between the two regimens. Adverse events were recorded by means of a patient diary and ECG monitoring.
Fifteen patients aged 40-74 years participated. Nilotinib PK following 200 mg BID taken with a meal strongly resembled that of 300 mg BID taken fasted (C percentile (P)10-P90: 665-1404 ng/mL and 557-1743 ng/mL, respectively). Meals delayed nilotinib absorption. Intra- and interpatient variability were not increased by intake with meals. Nilotinib with food was well tolerated.
With support of therapeutic drug monitoring, the use of a reduced 200 mg nilotinib dose with real-life meals seems feasible and safe. Future (confirmatory) studies should further explore the usefulness of nilotinib dosing together with food, including the relationship with treatment efficacy as well as long-term effects on quality of life.
NTR5000 (Netherlands Trial Register, www.trialregister.nl).
利用其食物依赖的生物利用度，本研究探讨了在慢性髓性白血病（CML）患者中，与实际餐食一起服用降低剂量对尼洛替尼药代动力学（PK）的影响。
尼洛替尼空腹（300mg BID，第 1-4 天）或与实际餐食（200mg BID，第 5-11 天）一起服用。丰富的采样（第 1、3、8、11 天）允许进行非房室 PK 分析。比较了两种方案之间尼洛替尼的暴露（AUC 0-C）及其个体内和个体间的变异性。通过患者日记和心电图监测记录不良反应。
15 名年龄在 40-74 岁的患者参与了研究。与空腹服用 300mg BID 相比，餐食服用 200mg BID 后的尼洛替尼 PK 非常相似（C 百分位（P）10-P90：665-1404ng/mL 和 557-1743ng/mL）。餐食延迟了尼洛替尼的吸收。个体内和个体间的变异性不因摄入食物而增加。尼洛替尼与食物一起服用时耐受性良好。
在治疗药物监测的支持下，与实际餐食一起使用降低剂量的 200mg 尼洛替尼似乎是可行且安全的。未来（确证性）研究应进一步探索尼洛替尼与食物一起给药的有效性，包括与治疗效果的关系以及对生活质量的长期影响。
NTR5000（荷兰试验注册中心，www.trialregister.nl）。
