38种CYP2C9基因型的酶活性在ibuprofen上
Ling-Jing Yuan1, Xiang-Yu Li2, Feng Ye3
1Department of Pharmacy, Shaoxing Second Hospital, Shaoxing, Zhejiang, China.
概括
这项研究研究了38种CYP2C9基因型如何影响ibuprofen代谢. 许多变体改变了布洛芬清除,突出显示了基因测试对于个性化缓解疼痛和减少药物不良反应的重要性.
科学领域:
- 药物基因组学 药物基因组学
- 药物新陈代谢 药物新陈代谢
- 酶动力学 酶动力学
背景情况:
- 布洛芬是一种广泛使用的无抗炎药物,用于治疗疼痛和发烧.
- 长期使用布洛芬可能会导致胃肠道出血和高血压等不良影响.
- CYP2C9基因多态性影响药物代谢和疗效.
研究的目的:
- 系统评估38种CYP2C9基因型对ibuprofen代谢的影响.
- 了解遗传变异如何影响ibuprofen的药理动力学特征.
- 为了确定潜在的低代谢者,容易产生不良药物反应.
主要方法:
- 再组合的人类CYP2C9微体酶 (38种变体) 被表达.
- 用布洛芬化系统评估酶活性.
- 代谢物含量通过高性能液体染色学 (HPLC) 量化.
- 动力参数使用迈凯利斯-门建模来确定.
主要成果:
- 与野生类型相比,八种CYP2C9变体在布洛芬清除中没有显著差异.
- 四种变体 (CYP2C9*38, *44, *53, *59) 的清除显著增加 (35%-230%).
- 与野生类型相比,26种变种显示出明显减少的清除率 (30% -99%).
结论:
- 这是对38种CYP2C9基因型和ibuprofen代谢的第一个全面研究.
- 结果补充了关于CYP2C9多态性和变异动态的现有知识.
- 识别差代谢器对于管理与布洛芬相关的药物暴露和风险至关重要.
相关概念视频
Factors Affecting Drug Biotransformation: Biological
180
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...
180
Nonlinear Pharmacokinetics: Dependence of Elimination Half-Life and Dose Clearance
208
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...
208
Phase I Reactions: Oxidation of Aliphatic and Aromatic Carbon-Containing Systems
239
Phase I biotransformation reactions are integral to drug metabolism, predominantly involving oxidative, reductive, and hydrolytic transformations. Chief among these are oxidative reactions, which enhance the hydrophilicity of xenobiotics and introduce polar functional groups to facilitate their elimination from the body.
Oxidation reactions are fundamental in aromatic carbon-containing systems. An example is the hydroxylation of phenobarbital, a process that transforms it into...
Oxidation reactions are fundamental in aromatic carbon-containing systems. An example is the hydroxylation of phenobarbital, a process that transforms it into...
239
Factors Affecting Drug Biotransformation: Physicochemical and Chemical Properties of Drugs
284
A drug's physicochemical properties fundamentally influence its metabolism. For instance, a drug's molecular size and shape critically determine its interaction with enzymes and transporters — larger drugs may face difficulty reaching enzyme active sites, altering their metabolic pathways. The pKa of a drug, which establishes its ionization state, can impact its solubility and absorption, thereby influencing metabolism.
The drug's acidity or basicity is essential in...
The drug's acidity or basicity is essential in...
284
Phase II Reactions: Glucuronidation
546
Glucuronidation, a pivotal phase II biotransformation process, involves the coupling of glucuronic acid to a drug or xenobiotic. Given its widespread occurrence and critical role in drug metabolism, it's considered the most crucial phase II reaction. It enhances the water solubility of substances, aiding their expulsion from the body. The driving force behind these reactions is a group of enzymes known as UDP-glucuronosyltransferases (UGTs). UGTs facilitate the transfer of a glucuronic acid...
546
Drug Metabolism: Phase I Reactions
3.4K
A phase I reaction is a biochemical process that introduces a functionally reactive polar group to a substance. This transformation predominantly occurs in the liver, facilitated by the cytochrome P450 system of hemoproteins situated in the lipophilic endoplasmic reticulum of cells. The metabolite generated through this process can have varying polarities. If it is sufficiently polar, it can be easily excreted in the urine due to its water compatibility. However, if the metabolite is nonpolar,...
3.4K


