ArticleCPT: pharmacometrics & systems pharmacology2018
PBPK Model of Morphine Incorporating Developmental Changes in Hepatic OCT1 and UGT2B7 Proteins to Explain the Variability in Clearances in Neonates and Small Infants.
Article in CPT: pharmacometrics & systems pharmacology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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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
21 citing papers in PubMed, 44 citations in OpenAlex.
- Preterm Physiologically Based Pharmacokinetic Model. Part II: Applications of the Model to Predict Drug Pharmacokinetics in the Preterm Population.Clinical pharmacokinetics · 2020Trial
- Ultrasound-guided suprazygomatic maxillary nerve blocks and perioperative opioid consumption in pediatric cleft palate repair: a retrospective cohort study.Scientific reports · 2026Observational
- Review of Precision Medicine and Diagnosis of Neonatal Illness.Diagnostics (Basel, Switzerland) · 2025Review
- Combining data on the bioavailability of midazolam and physiologically-based pharmacokinetic modeling to investigate intestinal CYP3A4 ontogeny.CPT: pharmacometrics & systems pharmacology · 2024Article
- The use of quantitative clinical pharmacology approaches to support moxidectin dosing recommendations in lactation.PLoS neglected tropical diseases · 2024Article
- Membrane transporters in drug development and as determinants of precision medicine.Nature reviews. Drug discovery · 2024Review
- Physiologically based pharmacokinetic modeling to predict the pharmacokinetics of codeine in different CYP2D6 phenotypes.Frontiers in pharmacology · 2024Article
- Physiologically Based Pharmacokinetic Modeling in Neonates: Current Status and Future Perspectives.Pharmaceutics · 2023Review
- Physiologically Based Pharmacokinetics Modeling in the Neonatal Population-Current Advances, Challenges, and Opportunities.Pharmaceutics · 2023Review
- Review
- Innovative approaches and recent advances in the study of ontogeny of drug metabolism and transport.British journal of clinical pharmacology · 2022Review
- Recent advances in the ontogeny of drug disposition.British journal of clinical pharmacology · 2022Review
- Quantitative Proteomics in Translational Absorption, Distribution, Metabolism, and Excretion and Precision Medicine.Pharmacological reviews · 2022Review
- Predicting Regional Respiratory Tissue and Systemic Concentrations of Orally Inhaled Drugs through a Novel PBPK Model.Drug metabolism and disposition: the biological fate of chemicals · 2022Article
- Teicoplanin physiologically based pharmacokinetic modeling offers a quantitative assessment of a theoretical influence of serum albumin and renal function on its disposition.European journal of clinical pharmacology · 2021Article
- Physiologically based pharmacokinetic/pharmacodynamic model for the prediction of morphine brain disposition and analgesia in adults and children.PLoS computational biology · 2021Article
- Potential implications of DMET ontogeny on the disposition of commonly prescribed drugs in neonatal and pediatric intensive care units.Expert opinion on drug metabolism & toxicology · 2021Review
- Hepatic Transporter Alterations by Nuclear Receptor Agonist T0901317 in Sandwich-Cultured Human Hepatocytes: Proteomic Analysis and PBPK Modeling to Evaluate Drug-Drug Interaction Risk.The Journal of pharmacology and experimental therapeutics · 2020Article
- Ontogeny of Hepatic Sulfotransferases and Prediction of Age-Dependent Fractional Contribution of Sulfation in Acetaminophen Metabolism.Drug metabolism and disposition: the biological fate of chemicals · 2019Article
- Making Medicines Baby Size: The Challenges in Bridging the Formulation Gap in Neonatal Medicine.International journal of molecular sciences · 2019Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
Morphine has large pharmacokinetic variability, which is further complicated by developmental changes in neonates and small infants. The impacts of organic cation transporter 1 (OCT1) genotype and changes in blood-flow on morphine clearance (CL) were previously demonstrated in children, whereas changes in UDP-glucuronosyltransferase 2B7 (UGT2B7) activity showed a small effect. This study, targeting neonates and small infants, was designed to assess the influence of developmental changes in OCT1 and UGT2B7 protein expression and modified blood-flow on morphine CL using physiologically based pharmacokinetic (PBPK) modeling. The implementation of these three age-dependent factors into the pediatric system platform resulted in reasonable prediction for an age-dependent increase in morphine CL in these populations. Sensitivity of morphine CL to changes in cardiac output increased with age up to 3 years, whereas sensitivity to changes in UGT2B7 activity decreased. This study suggests that morphine exhibits age-dependent extraction, likely due to the developmental increase in OCT1 and UGT2B7 protein expression/activity and hepatic blood-flow.
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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.