https://scholars.lib.ntu.edu.tw/handle/123456789/591924
標題: | Impact of Local Liver Irradiation Concurrent Versus Sequential with Lenvatinib on Pharmacokinetics and Biodistribution | 作者: | Tsai, Tung-Hu Chen, Yu-Jen LI-YING WANG Hsieh, Chen-Hsi |
關鍵字: | biodistribution; hepatocellular carcinoma; lenvatinib; pharmacokinetics; radiotherapy | 公開日期: | 30-三月-2021 | 出版社: | MDPI | 卷: | 13 | 期: | 7 | 來源出版物: | Cancers | 摘要: | 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 (AUClenvatinib) by 51.1% with three fractions of 2 Gy (RT2Gy×3f'x, p = 0.03), and 48.9% with RT9Gy×3f'x (p = 0.03). The AUClenvatinib increased by 148.8% (p = 0.008) with RT2Gy×3f'x, and 68.9% (p = 0.009) with RT9Gy×3f'x in the sequential regimen compared to the concurrent regimen. There were no differences in the AUClenvatinib between RT2Gy×3f'x and RT9Gy×3f'x in the concurrent or sequential regimen. Both the RT2Gy×3f'x and RT9Gy×3f'x concurrent regimens markedly decreased the biodistribution of lenvatinib in the heart, liver, lung, spleen, and kidneys, which ranged from 31% to 100% for RT2Gy×3f'x, and 11% to 100% for RT9Gy×3f'x, 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. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/591924 | ISSN: | 2072-6694 | DOI: | 10.3390/cancers13071598 |
顯示於: | 物理治療學系所 |
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