参麦注射液对达沙替尼药动学的影响:基于UPLC-MS/MS技术的深入体内分析

IF 1.8 4区 医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY
Weina Ma, Ling Li, Zhihui Li, Jungang Guo, Yifei Zhu, Liye Ge, Rong Wang, Lei Lv
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引用次数: 0

摘要

背景:达沙替尼已被广泛用于多种癌症的治疗,如肺癌和急性髓系白血病。参麦注射液是一种常用于抗肿瘤辅助治疗的中药注射剂。近年来,临床上越来越多地使用达沙替尼联合参麦注射液治疗肿瘤。然而,参麦注射液和达沙替尼联合使用的潜在风险和益处尚不清楚。目的:研究参麦注射液对达沙替尼药动学的潜在影响。方法:选取大鼠12只,随机分为达沙替尼单用组和达沙替尼联合参麦注射液组。为测定大鼠血浆中达沙替尼的浓度,取眼眶静脉血样。采用超高效液相色谱-串联质谱法测定达沙替尼的浓度,获得其药动学参数。结果:与达沙替尼单独给药相比,达沙替尼联合参麦注射液最大给药浓度(355.9±194.9比199.2±73.8 ng·mL-1)降低(P < 0.05)。矩曲线下面积(3867.0±2141.9比6355.3±3311.6 ng·mL-1·h2)、平均停留时间(3.7±1.2比6.5±3.1 h)均显著增加(P < 0.05)。结论:参麦注射液可能具有减缓达沙替尼吸收率的作用,延长达沙替尼在体内的滞留期,从而稳定血药浓度,减少药物不良反应。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Effects of Shenmai Injection on the Pharmacokinetics of Dasatinib: An In-Depth In vivo Analysis Utilizing UPLC-MS/MS Technique.

Background: Dasatinib has been widely used in the treatment of a variety of cancers, such as lung cancer and acute myeloid leukemia. Shenmai injection is a traditional Chinese medicine injection that is often used in antitumor adjuvant therapy. In recent years, dasatinib combined with Shenmai injection has been increasingly used to treat tumors clinically. However, the potential risks and benefits of co-administering Shenmai injection and dasatinib are unclear.

Objective: The study aimed to investigate the potential influence of Shenmai injection on dasatinib pharmacokinetics.

Methods: Twelve rats were selected and randomly divided into two groups: dasatinib alone and a combination of dasatinib and Shenmai injection. To measure the concentration of dasatinib in rat plasma, blood samples were obtained from the orbital vein. Using ultra-performance liquid chromatography-tandem mass spectrometry, the concentration of dasatinib was determined to obtain pharmacokinetic parameters.

Results: Compared to the dasatinib alone administration, the maximum concentration of the dasatinib plus Shenmai injection administration was decreased (355.9 ± 194.9 vs. 199.2 ± 73.8 ng·mL-1) (P < 0.05). Moreover, the area under the moment curve (3867.0 ± 2141.9 vs. 6355.3 ± 3311.6 ng·mL-1·h2) and mean residence time (3.7 ± 1.2 vs. 6.5 ± 3.1 h) showed a statistically significant increase (P < 0.05).

Conclusion: The study revealed that Shenmai injection might have the capacity to slow down the absorption rate of dasatinib and could extend the retention period of dasatinib in the body, resulting in stabilized blood drug concentrations and a reduction in adverse drug reactions.

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来源期刊
Current drug metabolism
Current drug metabolism 医学-生化与分子生物学
CiteScore
4.30
自引率
4.30%
发文量
81
审稿时长
4-8 weeks
期刊介绍: Current Drug Metabolism aims to cover all the latest and outstanding developments in drug metabolism, pharmacokinetics, and drug disposition. The journal serves as an international forum for the publication of full-length/mini review, research articles and guest edited issues in drug metabolism. Current Drug Metabolism is an essential journal for academic, clinical, government and pharmaceutical scientists who wish to be kept informed and up-to-date with the most important developments. The journal covers the following general topic areas: pharmaceutics, pharmacokinetics, toxicology, and most importantly drug metabolism. More specifically, in vitro and in vivo drug metabolism of phase I and phase II enzymes or metabolic pathways; drug-drug interactions and enzyme kinetics; pharmacokinetics, pharmacokinetic-pharmacodynamic modeling, and toxicokinetics; interspecies differences in metabolism or pharmacokinetics, species scaling and extrapolations; drug transporters; target organ toxicity and interindividual variability in drug exposure-response; extrahepatic metabolism; bioactivation, reactive metabolites, and developments for the identification of drug metabolites. Preclinical and clinical reviews describing the drug metabolism and pharmacokinetics of marketed drugs or drug classes.
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