代谢参数与华法林剂量之间的相关性在不同基因型的心脏置换患者中
Xiaowu Wang1, Diancai Zhao1, Jipeng Ma1
1Department of Cardiovascular Surgery, Xijing Hospital, Fourth Military Medical University, 710032 Xi'an, Shaanxi, China.
Reviews in cardiovascular medicine
|July 30, 2024
概括
心脏门置换患者的华法林剂量受身体表面积,基因型和尿酸水平的影响. 在这项研究中,肝脏和功能与华法林剂量没有显著的相关性.
科学领域:
- 药物基因组学 药物基因组学
- 临床药理学 临床药理学
- 心血管外科心血管外科
背景情况:
- 华法林是一种广泛用于终身治疗的抗凝剂,由于其有效性和成本效益.
- 它的抗凝效应受遗传因素,药物相互作用和饮食影响的变化.
- 维生素K环氧减少酶复合体1 (VKORC1) 和细胞染色体P450 2C9 (CYP2C9) 的遗传变异影响了华法林的剂量要求.
研究的目的:
- 调查影响心脏门置换患者华法林剂量的因素.
- 探索华法林剂量与不同基因型的肝功能,功能和尿酸水平之间的相关性.
- 在这个患者群体中建立华法林治疗的潜在剂量转换模型.
主要方法:
- 一项回顾性队列研究,涉及343名接受机械心脏门置换的患者.
- 基于CYP2C9和VKORC1基因型的华法林剂量的分析.
- 统计分析以确定华法林剂量与临床/代谢标志物之间的相关性,包括肝功能,功能和尿酸 (UA).
主要成果:
- 基因型分析显示,CYP2C9*1/*1和VKORC1AA基因型的患病率很高 (72.01%).
- 单变量分析表明,华法林维持剂量与性别,年龄,身体表面积 (BSA),UA和基因型之间存在显著的相关性.
- 多重线性回归确定了BSA,基因型和UA作为影响华法林剂量的独立因素;肝脏和脏功能没有显著的相关性.
结论:
- 尿酸含量在特定患者基因型 (CYP2C9*1/*1/VKORC1 GA+GG,CYP2C9*1/*1/VKORC1 AA) 中与华法林剂量有显著的相关性.
- 在心脏门置换患者中,BSA,基因型和UA是华法林剂量的关键决定因素.
- 这项研究强调了考虑遗传和代谢因素对于优化华法林治疗的重要性.
相关概念视频
Anticoagulant Drugs: Vitamin K Antagonists and Direct Oral Anticoagulants
1.2K
Oral anticoagulants are vital tools in preventing and treating blood clotting disorders. This diverse class of medications can be categorized as vitamin K antagonists, exemplified by warfarin, and direct thrombin inhibitors (DTIs), such as dabigatran, as well as factor Xa inhibitors, including rivaroxaban.
Warfarin, a prominent vitamin K antagonist family member, exerts its effect by inhibiting the enzyme VKORC1 (vitamin K epoxide reductase complex 1). By hindering this enzyme, warfarin...
Warfarin, a prominent vitamin K antagonist family member, exerts its effect by inhibiting the enzyme VKORC1 (vitamin K epoxide reductase complex 1). By hindering this enzyme, warfarin...
1.2K
Anticoagulant Drugs: Low-Molecular-Weight Heparins
659
Hemostasis is a crucial process that prevents excessive blood loss from damaged blood vessels. It involves various mechanisms such as vasoconstriction, platelet adhesion and activation, and fibrin formation. The importance of each mechanism depends on the type of vessel injury. In contrast, thrombosis is the abnormal formation of a blood clot within the blood vessels, leading to potential complications if the clot obstructs blood flow. Thrombosis can be caused by increased coagulability of the...
659
Determination of Michaelis Constant and Maximum Elimination Rate
83
The Michaelis constant (KM) and the theoretical maximum process rate (Vmax) are vital parameters in the Michaelis-Menten equation, central to many biochemical reactions. They provide essential insights into enzyme kinetics and drug metabolism.
These parameters can be estimated by analyzing plasma concentration data post-drug administration. A notable example of this application is phenytoin, a drug with capacity-limited kinetics. It's recommended that phenytoin should be administered at two...
These parameters can be estimated by analyzing plasma concentration data post-drug administration. A notable example of this application is phenytoin, a drug with capacity-limited kinetics. It's recommended that phenytoin should be administered at two...
83
Hepatic Drug Clearance: Effect of Protein Binding
182
Hepatic clearance is influenced by protein binding based on the drug's extraction ratio. Drugs with high extraction ratios are considered flow-limited and remain unaffected by protein binding during hepatic clearance. On the other hand, drugs with low extraction ratios may be impacted by plasma protein binding, although the extent of this influence depends on the fraction of the drug bound.
For low-extraction-ratio drugs that are less than 80% protein-bound, minor changes in protein binding...
For low-extraction-ratio drugs that are less than 80% protein-bound, minor changes in protein binding...
182
Nonlinear Pharmacokinetics: Dependence of Elimination Half-Life and Dose Clearance
110
The elimination half-life and drug clearance of drugs following nonlinear kinetics can vary with dosage. The Michaelis-Menten parameters and drug concentration influence these factors. As the dose increases, the elimination half-life tends to lengthen, resulting in a reduction in clearance and a disproportionately larger area under the curve. The total clearance can be derived from the Michaelis-Menten equation for drugs following a one-compartment model.
A study on guinea pigs examined the...
A study on guinea pigs examined the...
110
Factors Affecting Drug Biotransformation: Biological
135
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...
135


