ArticlePediatric research2015
The ontogeny of P-glycoprotein in the developing human blood-brain barrier: implication for opioid toxicity in neonates.
Article in Pediatric research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 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.
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Who cites it
45 citing papers in PubMed, 2 syntheses or guidelines pooled it, 95 citations in OpenAlex.
- A systematic review and an individual patient data meta-analysis of ivermectin use in children weighing less than fifteen kilograms: Is it time to reconsider the current contraindication?PLoS neglected tropical diseases · 2021Pooled it
- Safety of oral ivermectin during pregnancy: a systematic review and meta-analysis.The Lancet. Global health · 2020Pooled it
- Bayesian Population Pharmacokinetic Modeling of Ondansetron for Neonatal Opioid Withdrawal Syndrome.Clinical and translational science · 2025Trial
- The Pharmacokinetics and Pharmacodynamics of Buprenorphine in Neonatal Abstinence Syndrome.Clinical pharmacology and therapeutics · 2018Trial
- Advanced Drug Delivery in Pediatric Neurology: Developmental Barriers, Nanocarrier Strategies, and Translational Challenges.International journal of molecular sciences · 2026Review
- Why leave neonatal therapies up to chance?Pediatric research · 2026Article
- Advancements in Neonatal Brain Injury Treatment: Nanomedicine-Based Strategies.International journal of nanomedicine · 2026Review
- Perinatal Maturation of Drug Transporters and Claudin-5 at the Blood-Brain Barrier.CNS neuroscience & therapeutics · 2025Article
- Air pollution exposures and adverse childhood experiences in relation to sleep health in middle childhood.International journal of hygiene and environmental health · 2025Article
- The Development of an Age-Appropriate Fixed Dose Combination for Tuberculosis Using Physiologically-Based Pharmacokinetic Modeling (PBBM) and Risk Assessment.Pharmaceutics · 2024Article
- High-Dose Remifentanil Anesthesia With Minimal Sedation in Neonates: A Single-Center Retrospective Study.Cureus · 2024Article
- Challenges of pediatric pharmacotherapy: A narrative review of pharmacokinetics, pharmacodynamics, and pharmacogenetics.European journal of clinical pharmacology · 2024Review
- Physiologically Based Pharmacokinetic Modeling in Neonates: Current Status and Future Perspectives.Pharmaceutics · 2023Review
- Revisiting the concept of drug-resistant epilepsy: A TASK1 report of the ILAE/AES Joint Translational Task Force.Epilepsia · 2023Article
- Innovating spinal muscular atrophy models in the therapeutic era.Disease models & mechanisms · 2023Article
- Sensitivity to remifentanil and its predictive factor in male patients with moderate to severe obstructive sleep apnea syndrome.Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2023Article
- Effects of bacterial and viral pathogen-associated molecular patterns (PAMPs) on multidrug resistance (MDR) transporters in brain endothelial cells of the developing human blood-brain barrier.Fluids and barriers of the CNS · 2023Article
- Pharmacokinetics of Antimicrobials in Children with Emphasis on Challenges Faced by Low and Middle Income Countries, a Clinical Review.Antibiotics (Basel, Switzerland) · 2022Review
- Recent advances in the ontogeny of drug disposition.British journal of clinical pharmacology · 2022Review
- Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundNeonates have been shown to have a heightened sensitivity to the central depressive effects of opioids compared to older infants and adults. The limited development of P-glycoprotein (P-gp) may limit the ability of the neonate to efflux morphine from the brain back to the systemic circulation. The objective of the study was to determine the ontogeny of P-gp in the human brain.
methodsPostmortem cortex samples from gestational age (GA) 20-26 wk, GA 36-40 wk, postnatal age (PNA) 0-3 mo, PNA 3-6 mo, and adults were immunostained for P-gp.
resultsThe intensity of P-gp staining in adults was significantly higher compared to at GA 20-26 wk (P < 0.05), GA 36-40 wk (P < 0.05), and PNA 0-3 mo (P < 0.05). P-gp intensity at GA 20-26 wk (P < 0.05), GA 36-40 wk (P < 0.05), and PNA 0-3 mo (P < 0.05) was significantly lower compared to at PNA 3-6 mo.
conclusionP-gp expression in the brain is limited at birth, increases with postnatal maturation, and reaches adult levels at ~3-6 mo of age. Given the immaturity of blood-brain barrier (BBB) P-gp after birth, morphine may concentrate in the brain. This provides mechanistic support to life threatening opioid toxicity seen with maternal codeine use during breastfeeding.
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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.