ArticleDrug metabolism and disposition: the biological fate of chemicals2017
Age-Dependent Absolute Abundance of Hepatic Carboxylesterases (CES1 and CES2) by LC-MS/MS Proteomics: Application to PBPK Modeling of Oseltamivir In Vivo Pharmacokinetics in Infants.
Article in Drug metabolism and disposition: the biological fate of chemicals, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers, 1 of them a synthesis that pooled it.
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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
61 citing papers in PubMed, 1 synthesis or guideline pooled it, 101 citations in OpenAlex.
- Clinical Pharmacokinetics of Enalapril and Enalaprilat in Pediatric Patients-A Systematic Review.Frontiers in pediatrics · 2021Pooled it
- Population Pharmacokinetic Analysis of Enalapril and Enalaprilat in Newly Treated Children with Heart Failure: Implications for Safe Dosing of Enalapril (LENA Studies).Clinical pharmacokinetics · 2025Trial
- Population pharmacokinetics of selexipag for dose selection and confirmation in pediatric patients with pulmonary arterial hypertension.CPT: pharmacometrics & systems pharmacology · 2024Trial
- Dose Recommendation of Remimazolam Tosilate for General Anesthesia in Children and Adolescents: Synergistic Combination of PopPK and PBPK Approaches.Pharmaceutics · 2026Article
- Target Abundance in Pharmacological Target-Mediated Drug Disposition (TMDD) for Small Molecules - A Proteomics Approach.The AAPS journal · 2026Article
- Confounding Effect of Hepatic Carboxylesterase 1 (CES1) Variability on Clopidogrel Oxidation.Molecular pharmaceutics · 2025Article
- Remimazolam for successful sedation in children with left-to-right shunt congenital heart disease: An up-and-down sequential allocation trial.European journal of anaesthesiology · 2025Article
- Model-Informed Dose Optimization of Spironolactone in Neonates and Infants.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Kinetic analysis suggests that malathion at low environmental exposures is not toxic to humans.PloS one · 2025Article
- Transfer of Intravenous Remimazolam into Milk of Lactating Sheep and Uptake by Breast-fed Lambs.Current drug metabolism · 2025Article
- Article
- Very low enalapril and enalaprilat exposureFrontiers in pharmacology · 2025Article
- Physiologically-based pharmacokinetic modeling and simulation for initial dose optimization of levetiracetam in pediatrics.Frontiers in pharmacology · 2025Article
- Effective, but Safe? Physiologically Based Pharmacokinetic (PBPK)-Modeling-Based Dosing Study of Molnupiravir for Risk Assessment in Pediatric Subpopulations.ACS pharmacology & translational science · 2024Article
- Remimazolam anesthesia in pediatric patients undergoing cardiac catheterization for congenital heart disease: a retrospective observational study.Journal of anesthesia · 2024Observational
- Developmental Expression of Drug Transporters and Conjugating Enzymes Involved in Enterohepatic Recycling: Implication for Pediatric Drug Dosing.Clinical pharmacology and therapeutics · 2024Article
- Differential Tissue Abundance of Membrane-Bound Drug Metabolizing Enzymes and Transporter Proteins by Global Proteomics.Drug metabolism and disposition: the biological fate of chemicals · 2024Article
- Regulation of Human Hydrolases and Its Implications in Pharmacokinetics and Pharmacodynamics.Drug metabolism and disposition: the biological fate of chemicals · 2024Review
- Determining tissue distribution of the oral antileishmanial agent miltefosine: a physiologically-based pharmacokinetic modeling approach.Antimicrobial agents and chemotherapy · 2024Article
- Regulation of carboxylesterases and its impact on pharmacokinetics and pharmacodynamics: an up-to-date review.Expert opinion on drug metabolism & toxicology · 2024Review
1 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
8 authors at 4 institutions in 2 countries.
Funding
Abstract
The age-dependent absolute protein abundance of carboxylesterase (CES) 1 and CES2 in human liver was investigated and applied to predict infant pharmacokinetics (PK) of oseltamivir. The CES absolute protein abundance was determined by liquid chromatography-tandem mass spectrometry proteomics in human liver microsomal and cytosolic fractions prepared from tissue samples obtained from 136 pediatric donors and 35 adult donors. Two surrogate peptides per protein were selected for the quantification of CES1 and CES2 protein abundance. Purified CES1 and CES2 protein standards were used as calibrators, and the heavy labeled peptides were used as the internal standards. In hepatic microsomes, CES1 and CES2 abundance (in picomoles per milligram total protein) increased approximately 5-fold (315.2 vs. 1664.4) and approximately 3-fold (59.8 vs. 174.1) from neonates to adults, respectively. CES1 protein abundance in liver cytosol also showed age-dependent maturation. Oseltamivir carboxylase activity was correlated with protein abundance in pediatric and adult liver microsomes. The protein abundance data were then used to model in vivo PK of oseltamivir in infants using pediatric physiologically based PK modeling and incorporating the protein abundance-based ontogeny function into the existing pediatric Simcyp model. The predicted pediatric area under the curve, maximal plasma concentration, and time for maximal plasma concentration values were below 2.1-fold of the clinically observed values, respectively.
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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.