ArticleClinical pharmacokinetics2014
A re-evaluation and validation of ontogeny functions for cytochrome P450 1A2 and 3A4 based on in vivo data.
Article in Clinical pharmacokinetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 86 papers.
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Who cites it
86 citing papers in PubMed, 123 citations in OpenAlex.
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- Preterm Physiologically Based Pharmacokinetic Model. Part II: Applications of the Model to Predict Drug Pharmacokinetics in the Preterm Population.Clinical pharmacokinetics · 2020Trial
- Application of Pharmacometric Modelling Towards Precise Dosing in Neonates, Infants and Toddlers: A Scoping Review.Clinical pharmacokinetics · 2026Review
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- Simulation-Based Predictions to Support the Development of a Pediatric Fixed-Dose Combination of Dolutegravir/Emtricitabine/Tenofovir Alafenamide Fumarate.Clinical pharmacokinetics · 2026Review
- Advancing Pediatric Dose Scaling: Strategies, Modeling Approaches, and Clinical Applications.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Pharmacokinetics, Pharmacodynamics, and Safety of Single-Dose Luseogliflozin (TS-071) in Japanese Children and Adolescents With Type 2 Diabetes: A Multicenter, Open-Label, Parallel-Group Phase 1 Study.Clinical pharmacology in drug development · 2026Article
- Albumin and Other Plasma Proteins in Pediatric Patients: What, When, and How Much They Influence Antimicrobial Pharmacology.The journal of pediatric pharmacology and therapeutics : JPPT : the official journal of PPAG · 2026Article
- Population Physiologically-Based Pharmacokinetic Modeling to Determine Ontogeny: A Quantitative Clinical Pharmacology Example in Pediatric Rare Disease.CPT: pharmacometrics & systems pharmacology · 2026Review
- Mitotane dosage, plasma levels, and anthropometric measurements in pediatric adrenocortical carcinoma.Endocrine oncology (Bristol, England) · 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
- Development, Verification, and Application of a Chinese Pediatric Physiologically Based Pharmacokinetic Model: Emphasis on CYP Metabolism and Renal Elimination.The AAPS journal · 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
- Article
- Middle-Out Physiologically Based Pharmacokinetic Modeling to Support Pediatric Dosing Recommendation for Alectinib.CPT: pharmacometrics & systems pharmacology · 2025Article
- Model-Informed Once-Daily Dosing Strategy for Bedaquiline and Delamanid in Children, Adolescents and Adults with Tuberculosis.Clinical pharmacology and therapeutics · 2025Article
- Pharmacological treatment for apnoea of prematurity-the need for an individualised approach.Frontiers in pediatrics · 2025Review
- Interindividual variability in CYP3A-mediated venetoclax metabolism in vitro and in vivo in patients with chronic lymphocytic leukemia.Clinical and translational science · 2024Article
26 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
5 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND AND
objectivesCurrent cytochrome P450 (CYP) 1A2 and 3A4 ontogeny profiles, which are derived mainly from in vitro studies and incorporated in paediatric physiologically based pharmacokinetic models, have been reported to under-predict the in vivo clearances of some model substrates in neonates and infants.
methodWe report ontogeny functions for these enzymes as paediatric to adult relative intrinsic clearance per mg of hepatic microsomal protein, based on the deconvolution of in vivo pharmacokinetic data and by accounting for the impact of known clinical condition on hepatic unbound intrinsic clearance for caffeine and theophylline as markers of CYP1A2 activity and for midazolam as a marker of CYP3A4 activity.
resultsThe function for CYP1A2 describes an increase in relative intrinsic metabolic clearance from birth to 3 years followed by a decrease to adult values. The function for CYP3A4 describes a continuous rise in relative intrinsic metabolic clearance, reaching the adult value at about 1.3 years of age. The new models were validated by showing improved predictions of the systemic clearances of ropivacaine (major CYP1A2 substrate; minor CYP3A4 substrate) and alfentanil (major CYP3A4 substrate) compared with those using a previous ontogeny function based on in vitro data (alfentanil: mean squared prediction error 3.0 vs. 6.8; ropivacaine: mean squared prediction error 2.3 vs.14.2).
conclusionsWhen implementing enzyme ontogeny functions, it is important to consider potential confounding factors (e.g. disease) that may affect the physiological conditions of the patient and, hence, the prediction of net in vivo clearance.
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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.