Tsai Tung-Hu, Chen Yu-Jen, Wang Li-Ying, Hsieh Chen-Hsi
Institute of Traditional Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei 112, Taiwan.
Departments of Radiation Oncology, Mackay Memorial Hospital, Taipei 104, Taiwan.
Cancers (Basel). 2021 Mar 30;13(7):1598. doi: 10.3390/cancers13071598.
Concurrent and sequential regimens involving radiotherapy (RT) and lenvatinib were designed with off-target or stereotactic body radiation therapy (SBRT) doses in a freely moving rat model to evaluate the effect of RT on the pharmacokinetics (PK) of lenvatinib. Liver RT concurrent with lenvatinib decreased the area under the concentration-time curve of lenvatinib concentration (AUC) by 51.1% with three fractions of 2 Gy (RT, = 0.03), and 48.9% with RT ( = 0.03). The AUC increased by 148.8% ( = 0.008) with RT, and 68.9% ( = 0.009) with RT in the sequential regimen compared to the concurrent regimen. There were no differences in the AUC between RT and RT in the concurrent or sequential regimen. Both the RT and RT concurrent regimens markedly decreased the biodistribution of lenvatinib in the heart, liver, lung, spleen, and kidneys, which ranged from 31% to 100% for RT, and 11% to 100% for RT, compared to the sham regimen. The PK and biodistribution of lenvatinib can be modulated by simultaneous off-target irradiation and SBRT doses. The timing of lenvatinib administration with respect to RT, impacted the PK and biodistribution of the drug. Additionally, off-target and SBRT doses had a similar ability to modulate the effect of systemic therapy.
在自由活动的大鼠模型中，设计了涉及放疗（RT）和乐伐替尼的同步及序贯治疗方案，采用非靶向或立体定向体部放疗（SBRT）剂量，以评估放疗对乐伐替尼药代动力学（PK）的影响。乐伐替尼与肝脏放疗同步进行时，给予3次2 Gy的放疗剂量，乐伐替尼浓度 - 时间曲线下面积（AUC）降低了51.1%（P = 0.03）；给予放疗剂量时，AUC降低了48.9%（P = 0.03）。与同步治疗方案相比，序贯治疗方案中，给予放疗剂量时AUC增加了148.8%（P = 0.008），给予放疗剂量时AUC增加了68.9%（P = 0.009）。同步或序贯治疗方案中，放疗剂量和放疗剂量之间的AUC没有差异。与假手术组相比，放疗剂量和放疗剂量同步治疗方案均显著降低了乐伐替尼在心脏、肝脏、肺、脾脏和肾脏中的生物分布，放疗剂量降低的范围为31%至100%，放疗剂量降低的范围为11%至100%。乐伐替尼的药代动力学和生物分布可通过同时进行的非靶向照射和SBRT剂量进行调节。乐伐替尼给药时间相对于放疗的时机，会影响药物的药代动力学和生物分布。此外，非靶向和SBRT剂量在调节全身治疗效果方面具有相似的能力。
