在怀孕和产后期间,宫阴道液中埃法维伦兹暴露的药物遗传学
Oluwasegun Eniayewu1, Uche Azuka2, Jonah Ogah2
1Department of Pharmaceutical and Medicinal Chemistry, Faculty of Pharmaceutical Sciences, University of Ilorin, Ilorin, Nigeria.
Clinical pharmacology and therapeutics
|June 11, 2024
概括
怀孕和CYP2B6遗传变异显著影响子宫流体 (CVF) 中的埃法维伦兹水平. 怀孕期间,CVF中的efavirenz度较低,特别是在具有特定CYP2B6基因型的女性中.
科学领域:
- 药物动力学和药物基因组学
- 生殖健康和传染病.
背景情况:
- 抗逆转录病毒疗法 (ART) 对于治疗艾滋病毒至关重要,但药物的药理动力学可以因妊娠等生理变化而改变.
- 埃法维伦兹是一种常用的非核酸逆转录酶抑制剂 (NNRTI),用于ART疗法.
- 众所周知,遗传变异,特别是CYP2B6基因,会影响埃法维伦兹代谢和药物暴露.
研究的目的:
- 调查怀孕和CYP2B6遗传多态性对子宫流体 (CVF) 中的埃法维伦兹药理动力学的联合影响.
- 为了确定怀孕期间和产后期间CVF和血中efavirenz度.
- 评估CYP2B6 516G>T (rs3745274) 基因型与CVF中埃法维伦兹暴露之间的关联.
主要方法:
- 在尼日利亚 (2017-2020年) 进行的一项研究,涉及女性服用含 efavirenz 的 ART.
- 第一阶段:怀孕期间稀少采集CVF和血样本,以评估药物度和CYP2B6基因型相关性.
- 第二阶段:通过CYP2B6 516G>T基因型分层的参与者进行密集的药理动力学采样.
主要成果:
- CYP2B6 516G>T基因型与妊娠期间的 efavirenz CVF 度独立相关 (P=0.025).
- 在CVF中,艾法维伦兹度 (Cmin,Cmax,AUC0-24h) 的中位数在怀孕期间比分娩后更低.
- 在怀孕期间,Efavirenz清除在具有CYP2B6 516GT基因型的女性中较高,导致AUC和Cmax降低.
结论:
- 埃法维伦兹很好地分布在宫性阴道液中,其度通常超过蛋白质结合调整后的IC90.
- 怀孕和CYP2B6遗传多态性都显著影响CVF中efavirenz暴露.
- 研究结果强调需要个性化ART剂量策略,考虑到个体的遗传构成和生理状态.
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