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Atezolizumab in advanced hepatocellular carcinoma: good things come to those who wait.阿替利珠单抗治疗晚期肝细胞癌：好事多磨。
Immunotherapy. 2021 Jun;13(8):637-644. doi: 10.2217/imt-2021-0026. Epub 2021 Apr 6.
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Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries.《全球癌症统计数据 2020：全球 185 个国家和地区 36 种癌症的发病率和死亡率估计》。
CA Cancer J Clin. 2021 May;71(3):209-249. doi: 10.3322/caac.21660. Epub 2021 Feb 4.
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Pharmacokinetics and pharmacogenetics of sorafenib in patients with hepatocellular carcinoma: Implications for combination trials.索拉非尼在肝细胞癌患者中的药代动力学和药物遗传学：对联合试验的启示
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6
Systemic adjuvant treatment in hepatocellular carcinoma: tempted to do something rather than nothing.肝细胞癌的全身辅助治疗：倾向于采取行动而非无所作为。
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Sorafenib-associated hand-foot skin reaction: practical advice on diagnosis, mechanism, prevention, and management.索拉非尼相关手足皮肤反应：诊断、机制、预防和管理的实用建议。
Expert Rev Clin Pharmacol. 2019 Dec;12(12):1121-1127. doi: 10.1080/17512433.2019.1689122. Epub 2019 Nov 8.
8
Management of adverse events with tailored sorafenib dosing prolongs survival of hepatocellular carcinoma patients.个体化索拉非尼剂量调整治疗不良反应可延长肝癌患者的生存时间。
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在健康大鼠和肝癌荷瘤大鼠中索拉非尼代谢产物转化的药代动力学和表观米氏常数。

Pharmacokinetics and apparent Michaelis constant for metabolite conversion of sorafenib in healthy and hepatocellular carcinoma-bearing rats.

机构信息

School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, 310000, China.

Medical College of Jiaxing University, Key Laboratory of Medical Electronics & Digital Health of Zhejiang Province, Jiaxing University, Jiaxing, 314001, China.

出版信息

Bioanalysis. 2024;16(10):461-473. doi: 10.4155/bio-2023-0215. Epub 2024 Mar 26.

DOI:10.4155/bio-2023-0215
PMID:38530220
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11216244/
Abstract

Investigation of the pharmacokinetics of sorafenib (SRF) in rats with hepatocellular carcinoma (HCC). A reproducible ultra-HPLC-MS method for simultaneous determination of serum SRF, -hydroxymethyl sorafenib and -demethylation sorafenib. Both the maximum serum concentrations (2.5-times) and the area under the serum concentration-time curve from 0 h to infinity (4.5-times) of SRF were observed to be significantly higher, with a greater than 3.0-fold decrease in the clearance rate in the HCC-bearing rats compared with these values in healthy animals. Further study revealed approximately 3.8- and 3.2-times increases in the apparent Michaelis constant for -hydroxymethyl sorafenib and -demethylation sorafenib conversions in the HCC-bearing rats. The low efficiency for the SRF conversions was a key contributor to the increased serum concentrations of SRF.

摘要

肝癌荷瘤大鼠体内索拉非尼的药代动力学研究。一种重现性好的超高效液相色谱-串联质谱法，可同时测定血清中的索拉非尼、-羟甲基索拉非尼和-去甲基索拉非尼。与健康动物相比，荷瘤大鼠的索拉非尼最大血清浓度（2.5 倍）和 0 至无穷时的血清浓度-时间曲线下面积（4.5 倍）均显著升高，清除率降低超过 3.0 倍。进一步的研究表明，荷瘤大鼠中 -羟甲基索拉非尼和-去甲基索拉非尼转化的表观米氏常数分别增加了约 3.8 倍和 3.2 倍。索拉非尼转化效率低是导致其血清浓度升高的关键因素。