How to Manage Low Estriol Levels in Pregnancies, One Center Experience

Güleç, Elif Yılmaz; Gezdirici, Alper; Ayaz, Akif; Ozturk, Fatma Nihal; Polat, İbrahim

doi:10.4274/mmj.galenos.2022.22747

Cited by 4 publications

(1 citation statement)

References 28 publications

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“…It also regulates an important function during development; CYP3A7 metabolizes DHEA-S to 16α-hydroxy-DHEA-S (Kandel and Lampe 2021;Li and Lampe 2019;Kitada et al 1987;Torimoto et al 2007), and this metabolite is a precursor molecule to the production of estriol (Kandel and Lampe 2021;Li and Lampe 2019), a critically important hormone in bringing the pregnancy to full term (Chatuphonprasert, Jarukamjorn, and Ellinger 2018). Low estriol levels during the last trimester of pregnancy have been linked to both premature birth and low birth weight, two leading causes of infant mortality (YILMAZ GULEC et al 2022;Deng et al 2022).…”

Section: Introductionmentioning

confidence: 99%

HCV Antiviral Drugs Have the Potential to Adversely Perturb the Fetal-Maternal Communication Axis through Inhibition of CYP3A7 DHEA-S Oxidation

Work,

Hackett,

Lampe

2024

Drug Metab Dispos

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The hepatitis C virus (HCV) poses a great risk to pregnant people and their developing fetus, yet no HCV antiviral treatment guidelines have been established. While there has been a substantial increase in the development of HCV antivirals, the effect they have on the developing fetus remains poorly defined. Many of these drugs are metabolized through the cytochrome P450 CYP3A pathway, which is mediated by CYP3A7 in the fetus and developing infant. In this study, we sought to investigate the effect HCV antivirals have on CYP3A7 metabolism, as this CYP enzyme plays a vital role in proper fetal and neonatal development. Of the thirteen HCV antivirals we investigated, eight (~62%) inhibited CYP3A7 metabolic activity by 50% or more at a concentration of 20 µM. Furthermore, paritaprevir, asunaprevir, simeprevir, danoprevir, and glecaprevir all had observed half-maximal inhibitory concentrations between the range of 10-20 µM, which is physiologically relevant in comparison to the K m of DHEA-S oxidation (reported to be between 5 to 20 µM). We also discovered that paritaprevir is a timedependent inhibitor of CYP3A7, which shifts the IC 50 ~2-fold from 11 µM to 5 µM. Upon further characterization, paritaprevir inactivates DHEA-S metabolism by CYP3A7, with K I and K inact values of 4.66 µM and 0.00954 min -1 , respectively. Depending on treatment plan and off-label drug use, HCV treatment could adversely affect the fetal-maternal communication axis by blocking fetal CYP3A7 metabolism of important endogenous hormones.

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