ArticleCPT: pharmacometrics & systems pharmacology2018
First-Pass CYP3A-Mediated Metabolism of Midazolam in the Gut Wall and Liver in Preterm Neonates.
Article in CPT: pharmacometrics & systems pharmacology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 37 citations in OpenAlex.
- Midazolam for sedation of infants in the neonatal intensive care unit.The Cochrane database of systematic reviews · 2025Pooled it
- Preterm Physiologically Based Pharmacokinetic Model. Part II: Applications of the Model to Predict Drug Pharmacokinetics in the Preterm Population.Clinical pharmacokinetics · 2020Trial
- DDIapp-A Web-Based Application for Static Drug-Drug Interaction Assessment.CPT: pharmacometrics & systems pharmacology · 2026Article
- Human serum albumin: prediction model and reference values for preterm and term neonates.Pediatric research · 2026Article
- Deconvoluting Gut Versus Liver Cytochrome P450 3A4 Function: Drug Probes, Biomarkers, and Tissue Biopsy.Journal of clinical pharmacology · 2026Review
- Pharmacological therapy of neonatal analgosedation: current status, dilemmas, and perspectives.Frontiers in pediatrics · 2026Review
- Congenital tuberculosis in preterm infants in a high-burden setting in southwest China: a single-center cross-sectional study.Frontiers in pediatrics · 2025Article
- Combining data on the bioavailability of midazolam and physiologically-based pharmacokinetic modeling to investigate intestinal CYP3A4 ontogeny.CPT: pharmacometrics & systems pharmacology · 2024Article
- CBD and THC in Special Populations: Pharmacokinetics and Drug-Drug Interactions.Pharmaceutics · 2024Review
- The Use of Midazolam as an Antiseizure Medication in Neonatal Seizures: Single Center Experience and Literature Review.CNS & neurological disorders drug targets · 2024Observational
- Validation and application of a quantitative LC-MS/MS assay for the analysis of first-line anti-tuberculosis drugs, rifabutin and their metabolites in human breast milk.Journal of chromatography. B, Analytical technologies in the biomedical and life sciences · 2022Article
- Innovative approaches and recent advances in the study of ontogeny of drug metabolism and transport.British journal of clinical pharmacology · 2022Review
- Recent advances in the ontogeny of drug disposition.British journal of clinical pharmacology · 2022Review
- Bedaquiline exposure in pregnancy and breastfeeding in women with rifampicin-resistant tuberculosis.British journal of clinical pharmacology · 2022Article
- The Blind Spot of Pharmacology: A Scoping Review of Drug Metabolism in Prematurely Born Children.Frontiers in pharmacology · 2022Article
- Potential Applications of Chitosan-Based Nanomaterials to Surpass the Gastrointestinal Physiological Obstacles and Enhance the Intestinal Drug Absorption.Pharmaceutics · 2021Review
- Ontogeny of Drug-Metabolizing Enzymes.Methods in molecular biology (Clifton, N.J.) · 2021Review
- The Oral Bioavailability and Metabolism of Midazolam in Stable Critically Ill Children: A Pharmacokinetic Microtracing Study.Clinical pharmacology and therapeutics · 2021Article
- Inter-individual and inter-regional variations in enteric drug metabolizing enzyme activities: Results with cryopreserved human intestinal mucosal epithelia (CHIM) from the small intestines of 14 donors.Pharmacology research & perspectives · 2020Article
- Pharmacokinetics in children with chronic kidney disease.Pediatric nephrology (Berlin, Germany) · 2020Review
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
To predict first-pass and systemic cytochrome P450 (CYP) 3A-mediated metabolism of midazolam in preterm neonates, a physiological population pharmacokinetic model was developed describing intestinal and hepatic midazolam clearance in preterm infants. On the basis of midazolam and 1-OH-midazolam concentrations from 37 preterm neonates (gestational age 26-34 weeks) receiving midazolam orally and/or via a 30-minute intravenous infusion, intrinsic clearance in the gut wall and liver were found to be very low, with lower values in the gut wall (0.0196 and 6.7 L/h, respectively). This results in a highly variable and high total oral bioavailability of 92.1% (range, 67-95%) in preterm neonates, whereas this is around 30% in adults. This approach in which intestinal and hepatic clearance were separately estimated shows that the high bioavailability in preterm neonates is explained by, likely age-related, low CYP3A activity in the liver and even lower CYP3A activity in the gut wall.
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Registered trials
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