摘 要
心血管疾病是全球范围内导致死亡的主要原因之一，针对其治疗的心血管药物的药代动力学与药效学研究具有重要意义。本研究旨在深入探讨心血管药物在体内的吸收、分布、代谢和排泄过程（药代动力学）以及药物对机体产生的效应（药效学），为优化用药方案提供理论依据。采用高效液相色谱 - 质谱联用技术测定血药浓度，结合数学模型分析药代动力学参数；通过离体器官实验和整体动物实验评估药效学特征。结果表明，所研究的心血管药物在体内存在复杂的处置过程，不同个体间存在显著差异，这种差异与遗传因素、生理状态等密切相关。同时发现药物作用靶点明确，且剂量 - 效应关系呈现非线性特征，这为精准医疗提供了新的思路。创新之处在于建立了适用于心血管药物的个体化药代 - 药效学模型，该模型能够准确预测药物在特定人群中的行为，有助于制定个性化给药策略，提高临床疗效并减少不良反应发生率，为心血管疾病的合理用药研究开辟了新途径。
关键词：心血管药物；药代动力学；药效学；个体化模型；剂量-效应关系
Abstract
Cardiovascular diseases are one of the leading causes of death globally, making the pharmacokinetic and pharmacodynamic studies of cardiovascular drugs crucial for their treatment. This study aims to thoroughly investigate the absorption, distribution, me tabolism, and excretion (pharmacokinetics) of cardiovascular drugs in the body, as well as the effects these drugs have on the organism (pharmacodynamics), providing a theoretical basis for optimizing dosing regimens. High-performance liquid chromatography coupled with mass spectrometry was employed to measure drug concentrations in blood, while pharmacokinetic parameters were analyzed using mathematical models. Pharmacodynamic characteristics were evaluated through both ex vivo organ experiments and in vivo animal studies. The results indicate that the disposition of the studied cardiovascular drugs in the body is complex, with significant inter-individual variability closely related to genetic factors and physiological conditions. Additionally, it was found that the drug targets are specific, and the dose-effect relationship exhibits nonlinear features, offering new insights for precision medicine. An innovative aspect of this research is the establishment of an individualized pharmacokinetic-pharmacodynamic model tailored for cardiovascular drugs, which can accurately predict drug behavior in specific populations. This model aids in formulating personalized dosing strategies, enhancing clinical efficacy, and reducing the incidence of adverse reactions, thereby opening new avenues for rational drug use in cardiovascular disease.
Keywords：Cardiovascular Drugs；Pharmacokinetics；Pharmacodynamics；Individualized Model；Dose-Effect Relationship
目 录
引 言 1
第一章 心血管药物吸收机制研究 2
1.1 药物吸收途径分析 2
1.2 影响吸收的生理因素 2
1.3 吸收过程中的药物相互作用 3
第二章 心血管药物分布特性探讨 5
2.1 血浆蛋白结合率测定 5
2.2 组织分布特征分析 5
2.3 分布容积的影响因素 6
第三章 心血管药物代谢过程解析 8
3.1 主要代谢酶系研究 8
3.2 代谢产物鉴定与分析 8
3.3 药物代谢动力学模型 9
第四章 心血管药物排泄规律考察 11
4.1 排泄途径及其特点 11
4.2 肾功能对排泄的影响 11
4.3 排泄与药效的关系评估 12
结 论 13
参考文献 15
致 谢 16
心血管疾病是全球范围内导致死亡的主要原因之一，针对其治疗的心血管药物的药代动力学与药效学研究具有重要意义。本研究旨在深入探讨心血管药物在体内的吸收、分布、代谢和排泄过程（药代动力学）以及药物对机体产生的效应（药效学），为优化用药方案提供理论依据。采用高效液相色谱 - 质谱联用技术测定血药浓度，结合数学模型分析药代动力学参数；通过离体器官实验和整体动物实验评估药效学特征。结果表明，所研究的心血管药物在体内存在复杂的处置过程，不同个体间存在显著差异，这种差异与遗传因素、生理状态等密切相关。同时发现药物作用靶点明确，且剂量 - 效应关系呈现非线性特征，这为精准医疗提供了新的思路。创新之处在于建立了适用于心血管药物的个体化药代 - 药效学模型，该模型能够准确预测药物在特定人群中的行为，有助于制定个性化给药策略，提高临床疗效并减少不良反应发生率，为心血管疾病的合理用药研究开辟了新途径。
关键词：心血管药物；药代动力学；药效学；个体化模型；剂量-效应关系
Abstract
Cardiovascular diseases are one of the leading causes of death globally, making the pharmacokinetic and pharmacodynamic studies of cardiovascular drugs crucial for their treatment. This study aims to thoroughly investigate the absorption, distribution, me tabolism, and excretion (pharmacokinetics) of cardiovascular drugs in the body, as well as the effects these drugs have on the organism (pharmacodynamics), providing a theoretical basis for optimizing dosing regimens. High-performance liquid chromatography coupled with mass spectrometry was employed to measure drug concentrations in blood, while pharmacokinetic parameters were analyzed using mathematical models. Pharmacodynamic characteristics were evaluated through both ex vivo organ experiments and in vivo animal studies. The results indicate that the disposition of the studied cardiovascular drugs in the body is complex, with significant inter-individual variability closely related to genetic factors and physiological conditions. Additionally, it was found that the drug targets are specific, and the dose-effect relationship exhibits nonlinear features, offering new insights for precision medicine. An innovative aspect of this research is the establishment of an individualized pharmacokinetic-pharmacodynamic model tailored for cardiovascular drugs, which can accurately predict drug behavior in specific populations. This model aids in formulating personalized dosing strategies, enhancing clinical efficacy, and reducing the incidence of adverse reactions, thereby opening new avenues for rational drug use in cardiovascular disease.
Keywords：Cardiovascular Drugs；Pharmacokinetics；Pharmacodynamics；Individualized Model；Dose-Effect Relationship
目 录
引 言 1
第一章 心血管药物吸收机制研究 2
1.1 药物吸收途径分析 2
1.2 影响吸收的生理因素 2
1.3 吸收过程中的药物相互作用 3
第二章 心血管药物分布特性探讨 5
2.1 血浆蛋白结合率测定 5
2.2 组织分布特征分析 5
2.3 分布容积的影响因素 6
第三章 心血管药物代谢过程解析 8
3.1 主要代谢酶系研究 8
3.2 代谢产物鉴定与分析 8
3.3 药物代谢动力学模型 9
第四章 心血管药物排泄规律考察 11
4.1 排泄途径及其特点 11
4.2 肾功能对排泄的影响 11
4.3 排泄与药效的关系评估 12
结 论 13
参考文献 15
致 谢 16
