ArticleCPT: pharmacometrics & systems pharmacology2017
Characterization of Contributing Factors to Variability in Morphine Clearance Through PBPK Modeling Implemented With OCT1 Transporter.
Article in CPT: pharmacometrics & systems pharmacology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 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
30 citing papers in PubMed, 56 citations in OpenAlex.
- Morphine and hydromorphone pharmacokinetics in human volunteers: population-based modelling of interindividual and opioid-related variability.British journal of anaesthesia · 2025Trial
- Model-Informed Pediatric Dose Selection for Dapagliflozin by Incorporating Developmental Changes.CPT: pharmacometrics & systems pharmacology · 2021Trial
- Codeine toxicity via breast Milk: Can this occur and implications for opiate therapy in children.British journal of clinical pharmacology · 2026Review
- Evaluation of the Drug-Drug Interaction Potential of Cannabidiol Against UGT2B7-Mediated Morphine Metabolism Using Physiologically Based Pharmacokinetic Modeling.Pharmaceutics · 2024Article
- PBPK-PD model for predicting morphine pharmacokinetics, CNS effects and naloxone antagonism in humans.Acta pharmacologica Sinica · 2024Article
- Physiologically Based Pharmacokinetic (PBPK) Model Predictions of Disease Mediated Changes in Drug Disposition in Patients with Nonalcoholic Fatty Liver Disease (NAFLD).Pharmaceutical research · 2024Article
- Review
- 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
- Bridging the gap between in silico and in vivo by modeling opioid disposition in a kidney proximal tubule microphysiological system.Scientific reports · 2021Article
- Racial differences in opioid withdrawal syndrome among neonates with intrauterine opioid exposure.Pediatric research · 2021Observational
- Pharmacogenomics for Drug Dosing in Children: Current Use, Knowledge, and Gaps.Journal of clinical pharmacology · 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
- Physiologically-Based Pharmacokinetic Model of Morphine and Morphine-3-Glucuronide in Nonalcoholic Steatohepatitis.Clinical pharmacology and therapeutics · 2021Article
- Physiologically based pharmacokinetic/pharmacodynamic model for the prediction of morphine brain disposition and analgesia in adults and children.PLoS computational biology · 2021Article
- Application of Model Informed Precision Dosing to Address the Impact of Pregnancy Stage and CYP2D6 Phenotype on Foetal Morphine Exposure.The AAPS journal · 2021Article
- Use of normalized prediction distribution errors for assessing population physiologically-based pharmacokinetic model adequacy.Journal of pharmacokinetics and pharmacodynamics · 2020Article
- Physiologically-Based Pharmacokinetic Models for Evaluating Membrane Transporter Mediated Drug-Drug Interactions: Current Capabilities, Case Studies, Future Opportunities, and Recommendations.Clinical pharmacology and therapeutics · 2020Review
- Utilizing Pediatric Physiologically Based Pharmacokinetic Models to Examine Factors That Contribute to Methadone Pharmacokinetic Variability in Neonatal Abstinence Syndrome Patients.Journal of clinical pharmacology · 2020Article
- Electronic Health Record-Embedded Decision Support Platform for Morphine Precision Dosing in Neonates.Clinical pharmacology and therapeutics · 2020Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Morphine shows large interindividual variability in its pharmacokinetics; however, the cause of this has not been fully addressed. The variability in morphine disposition is considered to be due to a combination of pharmacogenetic and physiological determinants related to morphine disposition. We previously reported the effect of organic cation transporter (OCT1) genotype on morphine disposition in pediatric patients. To further explore the underlying mechanisms for variability arising from relevant determinants, including OCT1, a physiologically based pharmacokinetic (PBPK) model of morphine was developed. The PBPK model predicted morphine concentration-time profiles well, in both adults and children. Almost all of the observed morphine clearances in pediatric patients fell within a twofold range of median predicted values for each OCT1 genotype in each age group. This PBPK modeling approach quantitatively demonstrates that OCT1 genotype, age-related growth, and changes in blood flow as important contributors to morphine pharmacokinetic (PK) variability.
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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.