克洛札血度,CYP2D6 (*10, *2) 多态和不良反应风险之间的关联
Kankan Qu1, Qin Zhou1, Haohao Zhu1
1The Affiliated Mental Health Center of Jiangnan University, Wuxi Central Rehabilitation Hospital, Wuxi, Jiangsu, China.
Psychiatry and clinical psychopharmacology
|May 20, 2024
概括
细胞染色体P450 2D6的遗传变异会影响中国精神分裂症患者的克洛扎水平和不良反应. 基因型和药物监测可以帮助识别有风险的个体.
科学领域:
- 药物遗传学 药物遗传学
- 临床化学 临床化学
- 精神病学是一个精神病学.
背景情况:
- 克洛扎是治疗精神分裂症的重要抗精神病药物.
- 副作用和克洛扎的血度变化带来了临床挑战.
- 已知细胞染色体P450 2D6 (CYP2D6) 的遗传多态体会影响药物代谢.
研究的目的:
- 为了研究CYP2D6遗传多态性 (rs1065852 [*10]和rs16947 [*2]) 与克洛扎血度之间的关联.
- 探索克洛扎水平,CYP2D6基因型和不良反应风险之间的关系.
- 在中国的精神分裂症患者中建立克洛扎宾的治疗参考范围.
主要方法:
- 100名患有精神分裂症的中国住院患者的稳定状态克洛扎的血度使用二维液态染色学测量.
- 使用光 in situ 杂交,确定了 CYP2D6 [*10] 和 [*2] 多态.
- 副作用,包括白细胞,中性粒细胞,肌酸酶,氨酸转移酶和酸转移酶的变化,在6个月内进行了监测.
主要成果:
- 在克洛扎血度与白细胞/中性粒细胞数量下降以及肝酶升高之间发现了显著的线性关联.
- 患有CYP2D6*10TT和*2CC基因型的患者表现出克洛扎的血度最高 (P < .05).
- 与其他基因型相比, *10TT和 *2CC基因型患者的不良反应明显明显 (P < .05).
结论:
- CYP2D6 基因型鉴定和克洛扎宾的治疗药物监测是有价值的工具.
- 这些方法可以帮助识别患有更高风险的精神分裂症患者的克洛扎诱导的不良反应.
- 在中国患者中,克洛扎宾的治疗参考范围为102.5-483.1 ng/mL.
相关概念视频
Nonlinear Pharmacokinetics: Dependence of Elimination Half-Life and Dose Clearance
124
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...
124
Antipsychotic Drugs: Typical and Atypical Agents
185
Antipsychotic drugs are classified into first-generation (typical) drugs including phenothiazines; and second-generation (atypical) drugs. Chlorpromazine hydrochloride (Thorazine), a phenothiazine derivative, broadly impacts the central, autonomic, and endocrine systems. This drug, along with typical agents like haloperidol (Haldol), primarily works by antagonizing D2 receptors, thus reducing dopaminergic neurotransmission. However, typical antipsychotics can cause side effects such as sedation...
185
Psychosis: Goals of Pharmacotherapy
123
Antipsychotic drugs are a crucial treatment method for acute and chronic psychoses, bipolar illness, and behavioral disorders. The selection of these drugs depends on several factors, including the state of the disease, clinical judgment, possible drug interactions, and the patient's sensitivity to adverse effects. In immediate scenarios, such as delirium and dementia, short-term treatment with low doses of high-potency typical or atypical agents can effectively manage symptom exacerbation.
123
Pharmacovigilance
825
Post-marketing surveillance is a critical component of pharmaceutical regulation, often uncovering unanticipated adverse drug reactions (ADRs) once a drug is widely used over an extended period.
This process, termed pharmacovigilance, aims to detect, evaluate, and minimize harmful effects related to medication use. The data collection for pharmacovigilance depends on spontaneous reporting systems, where healthcare professionals or patients voluntarily report suspected ADRs.
In some cases, there...
This process, termed pharmacovigilance, aims to detect, evaluate, and minimize harmful effects related to medication use. The data collection for pharmacovigilance depends on spontaneous reporting systems, where healthcare professionals or patients voluntarily report suspected ADRs.
In some cases, there...
825
Drug Concentration Versus Time Correlation
735
The plasma drug concentration-time curve is a crucial tool in pharmacokinetics, representing the drug's concentration in plasma at different time intervals post-administration. This curve illustrates the drug's journey from absorption into the systemic circulation, distribution to body tissues, and eventual elimination through excretion or biotransformation.
Two pivotal parameters are the minimum effective concentration (MEC) and the minimum toxic concentration (MTC). The MEC is the...
Two pivotal parameters are the minimum effective concentration (MEC) and the minimum toxic concentration (MTC). The MEC is the...
735
Factors Affecting Protein-Drug Binding: Patient-Related Factors
57
Protein-drug binding, a pivotal aspect of pharmacokinetics, is subject to considerable variability influenced by an array of patient-related factors. The intricate interplay of age, individual differences, and pathological conditions significantly impact the binding dynamics and subsequent pharmacological effects.
Age stands as a key determinant in protein-drug binding. Neonates, characterized by low albumin content, experience heightened concentrations of unbound drugs such as phenytoin and...
Age stands as a key determinant in protein-drug binding. Neonates, characterized by low albumin content, experience heightened concentrations of unbound drugs such as phenytoin and...
57


