Prenatal efavirenz exposure is independently associated with maternal, but not fetal CYP2B6 genotype.

IF 1.7 3区医学 Q4 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Pharmacogenetics and genomics 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

Abstract

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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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。

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。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Pharmacogenetics and genomics 医学-生物工程与应用微生物

CiteScore

3.20

自引率

3.80%

发文量

审稿时长

3 months

期刊介绍： Pharmacogenetics and Genomics is devoted to the rapid publication of research papers, brief review articles and short communications on genetic determinants in response to drugs and other chemicals in humans and animals. The Journal brings together papers from the entire spectrum of biomedical research and science, including biochemistry, bioinformatics, clinical pharmacology, clinical pharmacy, epidemiology, genetics, genomics, molecular biology, pharmacology, pharmaceutical sciences, and toxicology. Under a single cover, the Journal provides a forum for all aspects of the genetics and genomics of host response to exogenous chemicals: from the gene to the clinic.