诺克洛巴萨姆度的升高和CYP2C19低代谢器表型中精神状态的改变:一个案例报告
Kristy M Phillips1, Josanna M Rodriguez-Lopez2, Andrew J Webb1
1Department of Pharmacy, Massachusetts General Hospital, Boston, MA, USA.
The Neurohospitalist
|September 13, 2023
概括
克罗巴萨姆 (一种二) 在 CYP2C19 酶功能不佳的个体中可能会引起严重的副作用. 这一案例凸显了低代谢者的诺克洛巴萨姆水平升高的风险,需要仔细的剂量和监测.
科学领域:
- 药物遗传学 药物遗传学
- 临床药理学 临床药理学
- 神经学 神经学
背景情况:
- 克洛巴萨姆是一种1,5-二,是一种常见的辅助疗法,用于耐火性发作和状态.
- 它的活性代谢物,诺克洛巴,由细胞染色体P450酶CYP2C19.9代谢.
- CYP2C19表现出显著的药物遗传变异性,影响药物清除和患者反应.
研究的目的:
- 报告亚裔美国男性因CYP2C19代谢受损而发生的克洛扎巴姆诱导昏迷病例.
- 为了强调CYP2C19药物遗传变异在用clobazam治疗的患者中的临床意义.
- 强调在药物剂量和管理中考虑遗传多态性的重要性.
主要方法:
- 一个亚裔美国男性患者的病例报告,患有发作障碍,接受了克洛巴萨姆治疗.
- 昏迷的临床观察和随后的诺克洛巴萨姆水平的实验室分析.
- 药物遗传测试以确定CYP2C19的基因型.
主要成果:
- 患者在接受标准治疗剂量clobazam时出现昏迷.
- 检测出显著增加的诺克洛巴赞度.
- 基因检测证实该患者的CYP2C19代谢能力较差,这解释了药物清除能力受损.
结论:
- 较差的CYP2C19代谢器表型会导致诺克洛巴萨姆的毒性水平,即使是标准的克洛巴萨姆剂量.
- 临床医生必须了解CYP2C19遗传多态化的风险人群.
- 建议根据包装标签或利用治疗药物监测调整克洛巴萨姆剂量,以防止不良事件.
更多相关视频
10:17High-throughput and Comprehensive Drug Surveillance Using Multisegment Injection-Capillary Electrophoresis-Mass Spectrometry
Published on: April 23, 2019
9.7K
07:04A High-performance Liquid Chromatography Measurement of Kynurenine and Kynurenic Acid: Relating Biochemistry to Cognition and Sleep in Rats
Published on: August 19, 2018
10.6K
相关概念视频
01:23Nonlinear Pharmacokinetics: Dependence of Elimination Half-Life and Dose Clearance
192
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...
192
01:22Nonlinear Pharmacokinetics: Causes of Nonlinearity
225
Nonlinearity in drug pharmacokinetics is caused by various factors influencing how a drug is absorbed, distributed, metabolized, and excreted. Understanding these nonlinear processes is crucial for predicting drug behavior in the body and optimizing drug dosing regimens.
Nonlinear drug absorption can occur when the process is rate-limited by solubility, carrier-mediated transport systems, or saturation of the presystemic gut wall or hepatic metabolism. For instance, high doses of riboflavin...
Nonlinear drug absorption can occur when the process is rate-limited by solubility, carrier-mediated transport systems, or saturation of the presystemic gut wall or hepatic metabolism. For instance, high doses of riboflavin...
225
01:20Antiepileptic Drugs: Potassium Channel Activators
210
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...
210
01:17Sedatives and Hypnotics Drugs: Miscellaneous Agents
200
Sedatives and hypnotics encompass a wide range of substances, each with its unique mechanism of action, uses, and potential adverse effects.
Melatonin congeners like ramelteon (Rozerem) and tasimelteon (Hetlioz) selectively bind to melatonin receptors (MT1 and MT2) and thus mimic the actions of melatonin, a hormone that regulates sleep-wake cycles. Tasimelteon is primarily used for non-24-hour sleep-wake disorder, common in blind patients. They are also used to treat conditions like insomnia...
Melatonin congeners like ramelteon (Rozerem) and tasimelteon (Hetlioz) selectively bind to melatonin receptors (MT1 and MT2) and thus mimic the actions of melatonin, a hormone that regulates sleep-wake cycles. Tasimelteon is primarily used for non-24-hour sleep-wake disorder, common in blind patients. They are also used to treat conditions like insomnia...
200
01:15Chronopharmacokinetics: Circadian Rhythms and Influence on Drug Response
87
Circadian rhythms are cyclic changes that are crucial in plasma drug concentrations. Various standard circadian parameters, including core body temperature, heart rate, and other cardiovascular factors, directly impact disease states and the therapeutic response to drug therapy.
The time of drug administration is an important factor to consider, as it can influence the toxic dose of a drug. For example, a study conducted by Prins et al. in 1997 examined the effects of the timing of...
The time of drug administration is an important factor to consider, as it can influence the toxic dose of a drug. For example, a study conducted by Prins et al. in 1997 examined the effects of the timing of...
87
01:16Hepatic Drug Excretion: Influencing Factors
152
The biliary system of the liver, crucial for bile secretion and drug excretion, comprises intrahepatic bile ducts that merge to form the common hepatic duct. This duct, carrying hepatic bile, combines with the cystic duct, draining the gallbladder and forming the common bile duct, which empties into the duodenum. Bile, produced by hepatic cells lining the bile canaliculi, is composed primarily of water, bile salts, pigments, electrolytes, and lesser amounts of cholesterol and fatty acids. Bile...
152