药物遗传对立体选择性稳定状态布鲁的处置的影响
Evan D Kharasch1, Eric J Lenze2
1Department of Anesthesiology, Duke University, Durham, North Carolina (E.D.K.); Bermaride, LLC (E.D.K.); and Department of Psychiatry, Washington University in St. Louis, St. Louis, Missouri (E.J.L.) evan.kharasch@duke.edu.
基因变异在CYP2B6显著影响布洛普的代谢和生物活化,影响药物度. 这一发现对于理解布洛普里昂的个体间变异性至关重要.
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
- 临床化学 临床化学
背景情况:
- 布普罗广泛用于治疗抑郁症,肥胖和戒烟.
- 布洛的新陈代谢和生物激活的个体间差异影响其治疗反应,耐受性和安全性.
- 已知细胞染色体P450 (CYP) 2B6的遗传变异会影响单剂量布洛普的氧化.
研究的目的:
- 调查CYP2B6,CYP2C19和P450氧化还原酶中的遗传多态性对布洛普反体平稳态处置的影响.
- 评估遗传变异对布洛及其主要代谢物度的影响.
- 为了确定是否存在对稳定状态布洛普的立体选择性处置的遗传影响.
主要方法:
- 对前性,随机,双盲,交叉研究的分析,比较品牌和仿制布洛 XL 300 mg.
- 衡量基因布洛及其代谢物的稳定状态反体血和尿液度.
- 在67名患有严重抑郁症的参与者中,对CYP2B6,CYP2C19和P450氧化降解酶的多态性进行基因定型.
主要成果:
- 在CYP2B6*6和CYP2B6 516G>T变异的载体中,两种布洛普对抗体的氧化显著降低.
- 这些CYP2B6变体的携带者表现出更高的布洛的血度和更低的氧.
- CYP2C19多态影响了较小的代谢途径,但没有影响布罗或氧的度,而P450氧化还原酶变体没有显著影响.
结论:
- 基因变异 CYP2B6 显著影响稳定状态新陈代谢和布洛的生物激活.
- 这些对布普罗皮安处置的遗传影响可能会导致治疗结果和安全性的个体间变化.
- 了解CYP2B6的基因型-表型关系对于优化布洛治疗至关重要.
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