抗发作药物的药物遗传变异和血度:系统性审查和元分析
Filip Milosavljevic1,2, Marina Manojlovic1, Lena Matkovic1,3
1Department of Physiology, Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia.
JAMA network open
|August 8, 2024
概括
基因变异在CYP2C9和CYP2C19显著增加类素水平,影响抗发作药物剂量. 其他变体对氨酸和卡巴马泽平产生较小影响,许多变体没有显著影响.
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
- 药物新陈代谢 药物新陈代谢
背景情况:
- 准确估计药物代谢能力对于个性化抗发作药物 (ASD) 剂量至关重要.
- 药物代谢酶的遗传变异可能会改变药物的血度,影响治疗的有效性和安全性.
研究的目的:
- 量化药物代谢酶中的遗传变异对常见抗发作药物的血度的影响.
- 为基因型引导的ASD剂量策略提供证据.
主要方法:
- 1990年至2023年间发表的98项研究 (12,543名参与者) 的系统综述和随机效应元分析.
- 包括的研究评估了氨酸,氨酸,拉莫特里金或卡巴马泽平,并进行基于基因型的子组分析.
- 用剂量规范化的AUC,Css或单剂量度分析了血度.
主要成果:
- 与低酶活性相关的CYP2C9和CYP2C19变体显著增加了伊的血度 (46%-56%).
- 在某些CYP2C9和CYP2C19变体的载体中,烯酸盐度增加了12%-20%.
- 卡巴马西平度在CYP3A5低代谢者中增加了12%;其他变体的影响很小或没有显著影响.
结论:
- CYP2C9和CYP2C19基因型显著影响氨酸的血水平,支持药物遗传学测试剂量个性化.
- 虽然一些变异会影响氨酸和碳胺度,但临床相关性往往是边际的.
- 许多药物遗传变异不会导致ASD血度的显著变化.
更多相关视频
相关概念视频
01:23Nonlinear Pharmacokinetics: Dependence of Elimination Half-Life and Dose Clearance
108
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...
108
01:20Antiepileptic Drugs: Modulators of Neurotransmitter Release Mediated by SV2A Protein
276
Antiepileptic drugs, such as levetiracetam (Keppra) and brivaracetam (Briviact), have emerged as crucial tools in managing epilepsy. These medications exert their therapeutic effects by targeting the synaptic vesicle protein SV2A, a transmembrane glycoprotein primarily found in the brain.
SV2A is a transmembrane glycoprotein located predominantly in the brain, modulating the release of neurotransmitters for neuronal communication. Both levetiracetam and brivaracetam exhibit a high affinity for...
SV2A is a transmembrane glycoprotein located predominantly in the brain, modulating the release of neurotransmitters for neuronal communication. Both levetiracetam and brivaracetam exhibit a high affinity for...
276
01:20Antiepileptic Drugs: Potassium Channel Activators
152
Ezocgabine or retigabine, an antiepileptic drug of remarkable efficacy, has revolutionized the management of seizures. It is a potassium channel activator, explicitly targeting the family of Q subtype potassium channels. It enhances the transmembrane potassium currents, regulating neuronal excitability. This action stabilizes the resting membrane potential, a pivotal factor in mitigating the hyperexcitability that characterizes epilepsy.
Ezogabine has gained approval as an adjunctive treatment...
Ezogabine has gained approval as an adjunctive treatment...
152
01:18Antiepileptic Drugs: GABAergic Pathway Potentiators
358
γ-aminobutyric acid or GABA, plays a pivotal role as an inhibitory neurotransmitter in the brain. GABA pathway potentiators, also known as GABAergic drugs, are a class of pharmaceutical agents designed to enhance the functioning of the GABAergic system. These medications primarily treat epilepsy, a neurological disorder characterized by recurrent seizures.
The key GABA pathway potentiators used in epilepsy management are as follows.
Benzodiazepines are a well-known class of drugs used for...
The key GABA pathway potentiators used in epilepsy management are as follows.
Benzodiazepines are a well-known class of drugs used for...
358
01:08Antiepileptic Drugs: Sodium Channel Blockers
472
Antiepileptic drugs are specialized medications that prevent seizures in individuals diagnosed with epilepsy. These drugs primarily function by blocking the movement of sodium ions through channels in the neuronal membrane, inhibiting the repetitive firing of action potentials often associated with seizures.
Sodium channel blockers modulate ion channels, particularly voltage-gated sodium channels. They block only sodium ion movement.
Among the most commonly prescribed antiepileptic drugs are...
Sodium channel blockers modulate ion channels, particularly voltage-gated sodium channels. They block only sodium ion movement.
Among the most commonly prescribed antiepileptic drugs are...
472
01:17Antiepileptic Drugs: Calcium Channel Blockers
350
Calcium channel blockers, a class of antiepileptic drugs, regulate the flow of calcium ions within neurons.
Calcium channel blockers exert their antiepileptic effects by targeting T-type calcium channels, which are integral to transmitting nerve signals in the central nervous system. These channels allow the passage of calcium ions, which are vital for neuronal communication. By inhibiting T-type calcium channels, calcium channel blockers effectively reduce the release of neurotransmitters and...
Calcium channel blockers exert their antiepileptic effects by targeting T-type calcium channels, which are integral to transmitting nerve signals in the central nervous system. These channels allow the passage of calcium ions, which are vital for neuronal communication. By inhibiting T-type calcium channels, calcium channel blockers effectively reduce the release of neurotransmitters and...
350