ArticleThe Journal of clinical investigation1999
Absence or pharmacological blocking of placental P-glycoprotein profoundly increases fetal drug exposure.
Article in The Journal of clinical investigation, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers, 2 of them syntheses 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.
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
68 citing papers in PubMed, 2 syntheses or guidelines pooled it, 355 citations in OpenAlex.
- Obstetric and neonatal outcomes following taxane use during pregnancy: a systematic review.BMC cancer · 2024Pooled it
- Fetal pharmacotherapy.Drugs · 2002Pooled it
- Review
- Changed expression of placental transporters and disrupted epigenetic patterns in a rat model of schizophrenia.Frontiers in pharmacology · 2025Article
- Placental efflux transporters and antiseizure or antidepressant medication use impact birth weight in MoBa cohort.iScience · 2024Article
- Changes in Expression and Function of Placental and Intestinal P-gp and BCRP Transporters during Pregnancy.International journal of molecular sciences · 2023Review
- Article
- Regulation of Placental Efflux Transporters during Pregnancy Complications.Drug metabolism and disposition: the biological fate of chemicals · 2022Review
- An update on placental drug transport and its relevance to fetal drug exposure.Medical review (2021) · 2022Review
- Predicting Human Fetal Drug Exposure Through Maternal-Fetal PBPK Modeling and In Vitro or Ex Vivo Studies.Journal of clinical pharmacology · 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
- Paclitaxel use in pregnancy: neonatal follow-up of infants with positive detection of intact paclitaxel and metabolites in meconium at birth.European journal of pediatrics · 2022Article
- Transfer of rhodamine-123 into the brain and cerebrospinal fluid of fetal, neonatal and adult rats.Fluids and barriers of the CNS · 2021Article
- Fetal Concentrations of Budesonide and Fluticasone Propionate: a Study in Mice.The AAPS journal · 2019Article
- Article
- Article
- Bisphenol A (BPA) and bisphenol S (BPS) alter the promoter activity of the ABCB1 gene encoding P-glycoprotein in the human placenta in a haplotype-dependent manner.Toxicology and applied pharmacology · 2018Article
- Lopinavir/ritonavir treatment increases the placental transfer of bupivacaine enantiomers in human immunodeficiency virus-infected pregnant women.British journal of clinical pharmacology · 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
8 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
It was recently shown that naturally occurring Mdr1a mutant fetuses of the CF-1 outbred mouse stock have no placental Mdr1a P-glycoprotein (P-gp) and that this absence is associated with increased sensitivity to avermectin, a teratogenic pesticide. To further define the role of placental drug-transporting P-gp in toxicological protection of the fetus, we used mice with a targeted disruption of the Mdr1a and Mdr1b genes. Mdr1a(+/-)/1b(+/-) females were mated with Mdr1a(+/-)/1b(+/-) males to obtain fetuses of 3 genotypes (Mdr1a(+/+)/1b(+/+), Mdr1a(+/-)/1b(+/-), and Mdr 1a(-/-)/1b(-/-)) in a single mother. Intravenous administration of the P-gp substrate drugs [(3)H]digoxin, [(14)C]saquinavir, or paclitaxel to pregnant dams revealed that 2.4-, 7-, or 16-fold more drug, respectively, entered the Mdr1a(-/-)/1b(-/-) fetuses than entered wild-type fetuses. Furthermore, placental P-gp activity could be completely inhibited by oral administration of the P-gp blockers PSC833 or GG918 to heterozygous mothers. Our findings imply that the placental drug-transporting P-gp is of great importance in limiting the fetal penetration of various potentially harmful or therapeutic compounds and demonstrate that this P-gp function can be abolished by pharmacological means. The latter principle could be applied clinically to improve pharmacotherapy of the unborn child.
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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 OpenQuestion graph.