ArticleDrug metabolism and disposition: the biological fate of chemicals2016
Developmental Expression of CYP2B6: A Comprehensive Analysis of mRNA Expression, Protein Content and Bupropion Hydroxylase Activity and the Impact of Genetic Variation.
Article in Drug metabolism and disposition: the biological fate of chemicals, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 3 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
36 citing papers in PubMed, 3 syntheses or guidelines pooled it, 45 citations in OpenAlex.
- Deprescribing Antidepressants in Children and Adolescents: A Systematic Review of Discontinuation Approaches, Cross-Titration, and Withdrawal Symptoms.Journal of child and adolescent psychopharmacology · 2025Pooled it
- Clinical Pharmacogenetics Implementation Consortium Guideline for CYP2B6 Genotype and Methadone Therapy.Clinical pharmacology and therapeutics · 2024Guideline
- Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2B6 and Efavirenz-Containing Antiretroviral Therapy.Clinical pharmacology and therapeutics · 2019Guideline
- Development and Evaluation of a Physiologically Based Pharmacokinetic Model for Cipepofol Across Diverse Clinical Populations.Pharmaceutics · 2026Article
- Developmental age and clinical illness driveFrontiers in pharmacology · 2026Article
- Physiologically Based Pharmacokinetic Modeling of Clobazam and Stiripentol Co-Therapy in Dravet Syndrome.Journal of personalized medicine · 2025Article
- Physiologically based pharmacokinetic modelling to predict artemether and lumefantrine exposure in neonates weighing less than 5 kg treated with artemether-lumefantrine to supplement the clinical data from the CALINA study.Tropical medicine and health · 2025Article
- Sub- and supratherapeutic efavirenz plasma concentrations with risk for HIV therapy failure are mainly genetically explained in Ugandan children: The prospective GENEFA cohort study.British journal of clinical pharmacology · 2025Article
- Physiologically Based Pharmacokinetics Modeling in the Neonatal Population-Current Advances, Challenges, and Opportunities.Pharmaceutics · 2023Review
- Association between CYP2B6 genetic variability and cyclophosphamide therapy in pediatric patients with neuroblastoma.Scientific reports · 2023Article
- Recent advances in the ontogeny of drug disposition.British journal of clinical pharmacology · 2022Review
- CYP2B6 allelic variants and non-genetic factors influence CYP2B6 enzyme function.Scientific reports · 2022Article
- Simultaneous absolute protein quantification of seven cytochrome P450 isoforms in rat liver microsomes by LC-MS/MS-based isotope internal standard method.Frontiers in pharmacology · 2022Article
- Clinical pharmacology and dosing regimen optimization of neonatal opioid withdrawal syndrome treatments.Clinical and translational science · 2021Review
- PharmVar GeneFocus: CYP2B6.Clinical pharmacology and therapeutics · 2021Review
- 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
- Sources of Interindividual Variability.Methods in molecular biology (Clifton, N.J.) · 2021Article
- Ontogeny of Drug-Metabolizing Enzymes.Methods in molecular biology (Clifton, N.J.) · 2021Review
- CYP2B6 Functional Variability in Drug Metabolism and Exposure Across Populations-Implication for Drug Safety, Dosing, and Individualized Therapy.Frontiers in genetics · 2021Review
- Impact of cytochrome P450 variation on meperidineXenobiotica; the fate of foreign compounds in biological systems · 2020Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Although CYP2B6 catalyzes the biotransformation of many drugs used clinically for children and adults, information regarding the effects of development on CYP2B6 expression and activity are scarce. Utilizing a large panel of human liver samples (201 donors: 24 fetal, 141 pediatric, and 36 adult), we quantified CYP2B6 mRNA and protein expression levels, characterized CYP2B6 (bupropion hydroxylase) activity in human liver microsomes (HLMs), and performed an extensive genotype analysis to differentiate CYP2B6 haplotypes such that the impact of genetic variation on these parameters could be assessed. Fetal livers contained extremely low levels of CYP2B6 mRNA relative to postnatal samples and fetal HLMs did not appear to catalyze bupropion hydroxylation; however, fetal CYP2B6 protein levels were not significantly different from postnatal levels. Considerable interindividual variation in CYP2B6 mRNA expression, protein levels, and activity was observed in postnatal HLMs (mRNA, ∼40,000-fold; protein, ∼300-fold; activity, ∼600-fold). The extremely wide range of interindividual variability in CYP2B6 expression and activity was significantly associated with age (P < 0.01) following log transformation of the data. Our data suggest that CYP2B6 activity appears as early as the first day of life, increases through infancy, and by 1 year of age, CYP2B6 levels and activity may approach those of adults. Surprisingly, CYP2B6 interindividual variability was not significantly associated with genetic variation in CYP2B6, nor was it associated with differences in gender or ethnicity, suggesting that factors other than these are largely responsible for the wide range of variability in CYP2B6 expression and activity observed among a large group of individuals/samples.
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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.