产前依非韦伦的暴露与母体而非胎儿的 CYP2B6 基因型独立相关。

IF 16.4 1区 化学 Q1 CHEMISTRY, MULTIDISCIPLINARY Accounts of Chemical Research Pub Date : 2024-10-01 Epub Date: 2024-06-24 DOI:10.1097/FPC.0000000000000542
Oluwasegun Eniayewu, Abdulafeez Akinloye, Babajide Shenkoya, Uche Azuka, Oluseye Bolaji, Ebunoluwa Adejuyigbe, Andrew Owen, Adeniyi Olagunju
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引用次数: 0

摘要

目的:了解胎儿和母体遗传学对产前药物暴露的影响有可能改善获益-风险评估。在这项研究中,我们调查了 CYP2B6 的两种功能多态性对依非韦伦产前暴露的影响:方法:从 HIV 阳性孕妇(112 人)及其分娩时的新生儿(107 人)中采集干血斑(DBS)样本。对这些样本进行了 CYP2B6 单核苷酸多态性基因分型。采用液相色谱-串联质谱法(LC-MS/MS)对依非韦伦进行定量分析:结果:母体和新生儿的依非韦伦浓度之间存在显著相关性(r = 0.46,R2 = 0.21,P 结论:母体和新生儿的依非韦伦浓度之间存在显著相关性(r = 0.46,R2 = 0.21,P 结论):所观察到的母体遗传对产前依非韦伦暴露的影响的临床意义有待进一步研究。
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Prenatal efavirenz exposure is independently associated with maternal, but not fetal CYP2B6 genotype.

Objectives: Understanding the influence of fetal and maternal genetics on prenatal drug exposure could potentially improve benefit-risk evaluation. In this study, we investigated the impact of two functional polymorphisms in CYP2B6 on prenatal exposure to efavirenz.

Methods: Dried blood spot (DBS) samples were collected from HIV-positive pregnant women ( n  = 112) and their newborns ( n  = 107) at delivery. They were genotyped for single nucleotide polymorphisms in CYP2B6. Efavirenz was quantified by liquid chromatography-tandem mass spectrometry (LC-MS/MS).

Results: Significant correlations were observed in efavirenz concentration between maternal and newborn ( r  = 0.46, R2  = 0.21, P  < 0.001), and maternal and cord ( r  = 0.83, R2  = 0.68, P  < 0.001) samples. Median (interquartile range) newborn plasma-to-maternal plasma and cord-to-maternal plasma ratios were 0.85 (0.03-3.49) and 0.78 (0.23-1.96), respectively. Newborn efavirenz concentration in DBS varied significantly based on composite maternal CYP2B6 genotype: fast ( CYP2B6 516GG and 983TT, n  = 26), 747 ng/ml (602-1060); intermediate ( CYP2B6 516GT or 983TC n  = 50), 1177 ng/ml (898-1765); and slow ( CYP2B6 516GT and 983TC or 516TT or 983CC, n  = 14), 3094 ng/ml (2126-3812). Composite newborn CYP2B6 genotype was, however, not significantly associated with prenatal exposure. Efavirenz concentration in newborn stratified as fast ( n  = 25), intermediate ( n  = 36), and slow metabolizers ( n  = 19) from prenatal exposure was 999.7 (774-1285), 1240 (709-1984), and 1792 ng/ml (1201-3188), respectively.

Conclusion: The clinical relevance of the observed influence of maternal genetics on prenatal efavirenz exposure requires further investigation.

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来源期刊
Accounts of Chemical Research
Accounts of Chemical Research 化学-化学综合
CiteScore
31.40
自引率
1.10%
发文量
312
审稿时长
2 months
期刊介绍: Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance. Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.
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