ArticleToxicology2015
Ontogenic expression of human carboxylesterase-2 and cytochrome P450 3A4 in liver and duodenum: postnatal surge and organ-dependent regulation.
Article in Toxicology, 2015. 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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Who cites it
21 citing papers in PubMed, 38 citations in OpenAlex.
- Renal maturation and catch-up clearance of ganciclovir in a preterm neonate: Bayesian pharmacokinetic analysis using a population model.Journal of pharmaceutical health care and sciences · 2025Article
- Combining data on the bioavailability of midazolam and physiologically-based pharmacokinetic modeling to investigate intestinal CYP3A4 ontogeny.CPT: pharmacometrics & systems pharmacology · 2024Article
- Regulation of carboxylesterases and its impact on pharmacokinetics and pharmacodynamics: an up-to-date review.Expert opinion on drug metabolism & toxicology · 2024Review
- 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
- Article
- Viral target and metabolism-based rationale for combined use of recently authorized small molecule COVID-19 medicines: Molnupiravir, nirmatrelvir, and remdesivir.Fundamental & clinical pharmacology · 2023Review
- Recent advances in the ontogeny of drug disposition.British journal of clinical pharmacology · 2022Review
- Covalent CES2 Inhibitors Protect against Reduced Formation of Intestinal Organoids by the Anticancer Drug Irinotecan.Current drug metabolism · 2022Article
- Potential Applications of Chitosan-Based Nanomaterials to Surpass the Gastrointestinal Physiological Obstacles and Enhance the Intestinal Drug Absorption.Pharmaceutics · 2021Review
- Oral delivery of peptide therapeutics in infants: Challenges and opportunities.Advanced drug delivery reviews · 2021Review
- Ontogeny of Drug-Metabolizing Enzymes.Methods in molecular biology (Clifton, N.J.) · 2021Review
- The Role of Metabolic Lipases in the Pathogenesis and Management of Liver Disease.Hepatology (Baltimore, Md.) · 2020Review
- Opinion on the re-evaluation of ascorbyl palmitate (E 304i) as a food additive in foods for infants below 16 weeks of age and the follow-up of its re-evaluation as a food additive for uses in foods for all population groups.EFSA journal. European Food Safety Authority · 2020Article
- Population pharmacokinetics of sildenafil in extremely premature infants.British journal of clinical pharmacology · 2019Article
- The Impact of Carboxylesterases in Drug Metabolism and Pharmacokinetics.Current drug metabolism · 2019Review
- A physiologically based pharmacokinetic and pharmacodynamic (PBPK/PD) model of the histone deacetylase (HDAC) inhibitor vorinostat for pediatric and adult patients and its application for dose specification.Cancer chemotherapy and pharmacology · 2017Article
- Oral drug absorption in pediatrics: the intestinal wall, its developmental changes and current tools for predictions.Biopharmaceutics & drug disposition · 2017Review
- 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.Drug metabolism and disposition: the biological fate of chemicals · 2017Article
- An update on the role of intestinal cytochrome P450 enzymes in drug disposition.Acta pharmaceutica Sinica. B · 2016Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Human carboxylesterase-2 (CES2) and cytochrome P450 3A4 (CYP3A4) are two major drug metabolizing enzymes that play critical roles in hydrolytic and oxidative biotransformation, respectively. They share substrates but may have opposite effect on therapeutic potential such as the metabolism of the anticancer prodrug irinotecan. Both CES2 and CYP3A4 are expressed in the liver and the gastrointestinal tract. This study was conducted to determine whether CES2 and CYP3A4 are expressed under developmental regulation and whether the regulation occurs differentially between the liver and duodenum. A large number of tissues (112) were collected with majority of them from donors at 1-198 days of age. In addition, multi-sampling (liver, duodenum and jejunum) was performed in some donors. The expression was determined at mRNA and protein levels. In the liver, CES2 and CYP3A4 mRNA exhibited a postnatal surge (1 versus 2 months of age) by 2.7 and 29 fold, respectively. CYP3A4 but not CES2 mRNA in certain pediatric groups reached or even exceeded the adult level. The duodenal samples, on the other hand, showed a gene-specific expression pattern at mRNA level. CES2 mRNA increased with age but the opposite was true with CYP3A4 mRNA. The levels of CES2 and CYP3A4 protein, on the other hand, increased with age in both liver and duodenum. The multi-sampling study demonstrated significant correlation of CES2 expression between the duodenum and jejunum. However, neither duodenal nor jejunal expression correlated with hepatic expression of CES2. These findings establish that developmental regulation occurs in a gene and organ-dependent manner.
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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.