ArticleMolecular pharmacology2008
Effect of pregnancy on cytochrome P450 3a and P-glycoprotein expression and activity in the mouse: mechanisms, tissue specificity, and time course.
Article in Molecular pharmacology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
48 citing papers in PubMed, 89 citations in OpenAlex.
- Population pharmacokinetics of lumefantrine in pregnant and non-pregnant women with uncomplicated Plasmodium falciparum malaria in Western Kenya.British journal of clinical pharmacology · 2026Article
- Plasma concentrations of doxorubicin and cyclophosphamide during anthracycline-based chemotherapy in a pregnant breast cancer patient: evaluation of gestational changes.Cancer chemotherapy and pharmacology · 2026Article
- Impact of sex and pregnancy on hepatic CYP3A4 expression and activity in a humanized mouse model.Drug metabolism and disposition: the biological fate of chemicals · 2025Article
- Estrogen associations with human pregnancy related increases in cytochrome P450 3A activity.Frontiers in pharmacology · 2025Article
- Forecasting Fetal Buprenorphine Exposure through Maternal-Fetal Physiologically Based Pharmacokinetic Modeling.Pharmaceutics · 2024Article
- Changes in Expression and Function of Placental and Intestinal P-gp and BCRP Transporters during Pregnancy.International journal of molecular sciences · 2023Review
- A cocktail probe approach to evaluate the effect of hormones on the expression and activity of CYP enzymes in human hepatocytes with conditions simulating late stage of pregnancy.European journal of clinical pharmacology · 2023Article
- Functioning of P-Glycoprotein during Pregnancy in Rabbits.Bulletin of experimental biology and medicine · 2023Article
- An update on the physiologic changes during pregnancy and their impact on drug pharmacokinetics and pharmacogenomics.Journal of basic and clinical physiology and pharmacology · 2022Review
- Applications, Challenges, and Outlook for PBPK Modeling and Simulation: A Regulatory, Industrial and Academic Perspective.Pharmaceutical research · 2022Review
- Limited Impact of Murine Placental MDR1 on Fetal Exposure of Certain Drugs Explained by Bypass Transfer Between Adjacent Syncytiotrophoblast Layers.Pharmaceutical research · 2022Article
- P-glycoprotein: new insights into structure, physiological function, regulation and alterations in disease.Heliyon · 2022Review
- Respiratory depression in a neonate born to mother on maximum dose sertraline: a case report.Journal of medical case reports · 2021Article
- Pregnancy-Related Hormones Increase Nifedipine Metabolism in Human Hepatocytes by Inducing CYP3A4 Expression.Journal of pharmaceutical sciences · 2021Article
- Impact of Microbiome on Hepatic Metabolizing Enzymes and Transporters in Mice during Pregnancy.Drug metabolism and disposition: the biological fate of chemicals · 2020Article
- Methods to study mechanisms underlying altered hepatic drug elimination during pregnancy.Seminars in perinatology · 2020Review
- Fetal Concentrations of Budesonide and Fluticasone Propionate: a Study in Mice.The AAPS journal · 2019Article
- Pharmacokinetics of HIV-Integrase Inhibitors During Pregnancy: Mechanisms, Clinical Implications and Knowledge Gaps.Clinical pharmacokinetics · 2019Review
- Temporal transcriptomic analysis of metabolic genes in maternal organs and placenta during murine pregnancy.Biology of reproduction · 2018Article
- An update on expression and function of P-gp/ABCB1 and BCRP/ABCG2 in the placenta and fetus.Expert opinion on drug metabolism & toxicology · 2018Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
The plasma concentrations of orally administered anti-human immunodeficiency virus protease inhibitors are significantly reduced during human and mouse pregnancy. We have shown that in the mouse, at gestational day 19, this reduction is due to increased hepatic cytochrome P450 3a (Cyp3a) protein expression and activity. In the current study, we investigated the mechanisms by which Cyp3a activity is increased by pregnancy and the time course of change in expression of Cyp3a and P-glycoprotein (P-gp) in various tissues. We found that hepatic transcripts of Cyp3a16, Cyp3a41, and Cyp3a44 were significantly increased during pregnancy, whereas those of Cyp3a11 and Cyp3a25 were significantly decreased. This resulted in a net increase in Cyp3a protein expression and activity in the liver during pregnancy. The increase in Cyp3a41 and Cyp3a44 transcripts was positively correlated (p < 0.05) with hepatocyte nuclear factor 6 and estrogen receptor-alpha transcripts. The pregnancy-related factors that transcriptionally activated mouse Cyp3a isoforms also activated the human CYP3A4 promoter in pregnant CYP3A4-promoter-luciferase transgenic (CYP3A4-tg) mice. In contrast, intestinal Cyp3a protein expression was not significantly affected by pregnancy. No change in P-gp protein expression was observed in the liver or kidney during pregnancy, although a significant decrease was observed in the placenta. Because hepatic CYP3A activity also seems to be induced during human pregnancy, the mouse (including CYP3A4-tg mouse) seems to be an excellent animal model to determine the molecular mechanisms for such an induction.
Indexed as
Identifiers
What OpenQuestion holds
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 OpenQuestion graph.