ArticleJournal of pharmaceutical sciences2021
Pregnancy-Related Hormones Increase Nifedipine Metabolism in Human Hepatocytes by Inducing CYP3A4 Expression.
Article in Journal of pharmaceutical sciences, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
14 citing papers in PubMed, 1 synthesis or guideline pooled it, 29 citations in OpenAlex.
- Applications of Exosomes in Female Medicine: A Systematic Review of Molecular Biology, Diagnostic and Therapeutic Perspectives.International journal of molecular sciences · 2026Pooled it
- Pregnancy-related effect on elexacaftor, tezacaftor and ivacaftor pharmacokinetics in women with cystic fibrosis.British journal of clinical pharmacology · 2026Observational
- The biology, function, and applications of exosomes as novel biomarkers forFrontiers in pharmacology · 2026Review
- Mechanisms of altered hepatic drug disposition during pregnancy: small molecules.Expert opinion on drug metabolism & toxicology · 2025Review
- Estrogen associations with human pregnancy related increases in cytochrome P450 3A activity.Frontiers in pharmacology · 2025Article
- Physiologically Based Pharmacokinetic Modeling in Pregnancy, during Lactation and in Neonates: Achievements, Challenges and Future Directions.Pharmaceutics · 2024Article
- The effect of pregnancy-related hormones on hepatic transporters: studies with premenopausal human hepatocytes.Frontiers in pharmacology · 2024Article
- Review
- Utility of Physiologically Based Pharmacokinetic Modeling to Investigate the Impact of Physiological Changes of Pregnancy and Cancer on Oncology Drug Pharmacokinetics.Pharmaceutics · 2023Article
- Physiologic Changes During Pregnancy and Impact on Small-Molecule Drugs, Biologic (Monoclonal Antibody) Disposition, and Response.Journal of clinical pharmacology · 2023Review
- Pregnancy related hormones increase CYP3A mediated buprenorphine metabolism in human hepatocytes: a comparison to CYP3A substrates nifedipine and midazolam.Frontiers in pharmacology · 2023Article
- Impact of pregnancy related hormones on drug metabolizing enzyme and transport protein concentrations in human hepatocytes.Frontiers in pharmacology · 2022Article
- The Impact of Pregnancy on Antihypertensive Drug Metabolism and Pharmacokinetics: Current Status and Future Directions.Expert opinion on drug metabolism & toxicology · 2021Review
- Pregnancy-Related Hormones Increase UGT1A1-Mediated Labetalol Metabolism in Human Hepatocytes.Frontiers in pharmacology · 2021Article
Corrections and comments
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Authors and funding
14 authors at 1 institution in 1 country.
Funding
Abstract
Pregnancy-related hormones (PRH) have emerged as key regulators of hepatic cytochrome P450 (CYP) enzyme expression and function. The impact of PRH on protein levels of CYP3A4 and other key CYP enzymes, and the metabolism of nifedipine (a CYP3A4 substrate commonly prescribed during pregnancy), was evaluated in primary human hepatocytes. Sandwich-cultured human hepatocytes (SCHH) from female donors were exposed to PRH (estradiol, estriol, estetrol, progesterone, and cortisol), individually or in combination as a cocktail. Absolute protein concentrations of twelve CYP isoforms in SCHH membrane fractions were quantified by nanoLC-MS/MS, and metabolism of nifedipine to dehydronifedipine in SCHH was evaluated. PRH significantly increased CYP3A4 protein concentrations and nifedipine metabolism to dehydronifedipine in a concentration-dependent manner. CYP3A4 mRNA levels in hepatocyte-derived exosomes positively correlated with CYP3A4 protein levels and dehydronifedipine formation in SCHH. PRH also increased CYP2B6, CYP2C8 and CYP2A6 levels. Our findings demonstrate that PRH increase nifedipine metabolism in SCHH by inducing CYP3A4 expression and alter expression of other key CYP proteins in an isoform-specific manner, and suggest that hepatocyte-derived exosomes warrant further investigation as biomarkers of hepatic CYP3A4 metabolism. Together, these results offer mechanistic insight into the increases in nifedipine metabolism and clearance observed in pregnant women.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.