霍诺基奥尔对abemaciclib代谢的作用,在体外和体内都有
Tian Yang1, Wei Song2, Zebei Lu3
1Comprehensive Breast Health Center, Department of Thyroid and Breast Surgery, Institute of Breast Cancer, Lishui Hospital of Wenzhou Medical University, The First Affiliated Hospital of Lishui University, Lishui People's Hospital, 15 Dazhong Road, Lishui, Zhejiang 323000, China.
The Journal of pharmacy and pharmacology
|November 10, 2025
概括
红醇显著改变了abemaciclib的药理动力学,增加了其暴露,并延长了其在体内存在的时间. 这表明显著的药物相互作用需要谨慎在同时使用这些化合物.
科学领域:
- 药理学 药理学是指药理学的学科.
- 药物新陈代谢 药物新陈代谢
- 在瘤学瘤学.
背景情况:
- 药物相互作用 (DDI) 可以显著影响药物的疗效和药理动力学.
- 阿贝马西克利布是一种CDK4/6抑制剂,用于治疗雌激素受体阳性乳腺癌.
- 红是一种植物化学物质,表现出抗癌性质.
研究的目的:
- 为了研究红醇在体外和体内对abemaciclib的药理动力学的影响.
- 评估Honokiol和abemaciclib之间的潜在药物相互作用.
主要方法:
- 使用大鼠肝脏显微体 (RLMs) 进行体外研究以确定IC50值.
- 在Sprague-Dawley大鼠的体内药理动力学研究中,使用单剂和多剂量Honokiol.
- 使用UPLC/MS-MS量化abemaciclib血的度.
- 分子对接以分析与CYP3A4.4的结合相互作用.
主要成果:
- 在RLMs中,Honokiol对abemaciclib代谢的IC50为27.6μM.
- 同时服用霍诺基显著增加了abemaciclib在血度-时间曲线下的面积和平均停留时间.
- 霍诺基尔降低了abemaciclib的清除值 (CLz/F),并延长了其最大度 (Cmax) 和达到最大度 (Tmax) 的时间.
- 分子对接表明通过ALA370结合部位对CYP3A4酶进行竞争.
结论:
- 霍诺基醇和阿贝马西利布在体外和体内有显著的药物相互作用.
- 同时服用霍诺基奥尔和阿贝马西克利布需要仔细考虑,因为药理动力学发生了变化.
- 需要对接受Honokiol和abemaciclib.lib两种药物的患者给予进一步的注意.
相关概念视频
Methods for Studying Drug Absorption: In vitro
562
In vitro experiments are crucial for understanding the transport and absorption of drugs through biological materials. These studies employ varied methods such as the diffusion cell method, the everted sac technique, and the everted ring technique.
The diffusion cell method uses a two-compartment cell, including a donor compartment with the drug solution, which simulates the environment where the drug is applied, and a receptor compartment with a buffer solution, which simulates the environment...
The diffusion cell method uses a two-compartment cell, including a donor compartment with the drug solution, which simulates the environment where the drug is applied, and a receptor compartment with a buffer solution, which simulates the environment...
562
Inhibition of Cdk Activity
5.5K
The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
5.5K
Bioavailability: Influencing Factors
322
Bioavailability refers to the extent and rate at which a drug reaches systemic circulation in its active form. Extent refers to the amount of the drug that makes it into circulation, while rate is the speed at which it enters circulation. It is influenced by several factors critical for optimizing drug formulations, dosing regimens, and therapeutic outcomes.Physicochemical properties of drugs and formulationsThe solubility, stability, and dissolution rate of a drug significantly impact its...
322
Measurement of Bioavailability: Pharmacodynamic Methods
225
Pharmacodynamic methods provide insights into a drug's effects on physiological processes over time and play a crucial role in understanding bioavailability and therapeutic efficacy. These methods can be broadly classified into acute pharmacological and therapeutic response approaches, each with distinct mechanisms and applications.The acute pharmacological response method directly correlates a drug's physiological effects, such as ECG or pupil diameter changes, to its time course in the body.
225
Factors Affecting Drug Biotransformation: Biological
503
Biological factors significantly impact drug metabolism, influencing drug clearance, efficacy, and potential toxicity.
Species differences: Variations in enzyme systems across species can cause disparities in drug metabolism. For instance, humans may metabolize certain drugs faster than rodents, altering therapeutic effects.
Strain differences: Genetic variations within a species can result in differing enzyme activity, impacting drug response and toxicity. For example, some mouse strains may...
Species differences: Variations in enzyme systems across species can cause disparities in drug metabolism. For instance, humans may metabolize certain drugs faster than rodents, altering therapeutic effects.
Strain differences: Genetic variations within a species can result in differing enzyme activity, impacting drug response and toxicity. For example, some mouse strains may...
503
Drug Biotransformation: Overview
3.5K
Pharmaceutical substances known as xenobiotics are predominantly lipophilic and nonionized. This enables them to permeate lipid bilayers, such as cell membranes, and interact with intracellular target receptors. Lipophilic drugs have an advantage in crossing biological barriers and reaching their intended sites of action. However, lipophilic drugs often have a restricted capacity for renal expulsion or elimination from the body. When these drugs enter the kidneys and undergo glomerular...
3.5K


