ArticleEuropean journal of clinical pharmacology2010
Ontogeny of midazolam glucuronidation in preterm infants.
Article in European journal of clinical pharmacology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 28 citations in OpenAlex.
- Recently Registered Midazolam Doses for Preterm Neonates Do Not Lead to Equal Exposure: A Population Pharmacokinetic Model.Journal of clinical pharmacology · 2019Trial
- The Use of Midazolam as an Antiseizure Medication in Neonatal Seizures: Single Center Experience and Literature Review.CNS & neurological disorders drug targets · 2024Observational
- The Blind Spot of Pharmacology: A Scoping Review of Drug Metabolism in Prematurely Born Children.Frontiers in pharmacology · 2022Article
- The Oral Bioavailability and Metabolism of Midazolam in Stable Critically Ill Children: A Pharmacokinetic Microtracing Study.Clinical pharmacology and therapeutics · 2021Article
- Proof of Concept: First Pediatric [Clinical pharmacology and therapeutics · 2020Article
- Dose-linearity of the pharmacokinetics of an intravenous [British journal of clinical pharmacology · 2019Article
- Treating Chronic Pain: An Overview of Clinical Studies Centered on the Buprenorphine Option.Drugs · 2018Review
- Pharmacokinetics in neonatal prescribing: evidence base, paradigms and the future.British journal of clinical pharmacology · 2015Review
- The interplay between drugs and the kidney in premature neonates.Pediatric nephrology (Berlin, Germany) · 2014Review
- Clinical pharmacology of midazolam in neonates and children: effect of disease-a review.International journal of pediatrics · 2014Review
Corrections and comments
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Authors and funding
5 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeIn preterm infants, the biotransformation of midazolam (M) to 1-OH-midazolam (OHM) by cytochrome P450 3A4 (CYP3A4) is developmentally immature, but it is currently unknown whether the glucuronidation of OHM to 1-OH-midazolam glucuronide (OHMG) is also decreased. The aim of our study was to investigate the urinary excretion of midazolam and its metabolites OHM and OHMG in preterm neonates following the intravenous (IV) or oral (PO) administration of a single M dose.
methodsPreterm infants (post-natal age 3-13 days, gestational age 26-34 4/7 weeks) scheduled to undergo a stressful procedure received a 30-min IV infusion (n = 15) or a PO bolus dose (n= 7) of 0.1 mg/kg midazolam. The percentage of midazolam dose excreted in the urine as M, OHM and OHMG up to 6 h post-dose was determined.
resultsThe median percentage of the midazolam dose excreted as M, OHM and OHMG in the urine during the 6-h interval after the IV infusion was 0.44% (range 0.02-1.39%), 0.04% (0.01-0.13%) and 1.57% (0.36-7.7%), respectively. After administration of the PO bolus dose, the median percentage of M, OHM and OHMG excreted in the urine was 0.11% (0.02-0.59%), 0.02% (0.00-0.10%) and 1.69% (0.58-7.31%), respectively. The proportion of the IV midazolam dose excreted as OHMG increased significantly with postconceptional age (r = 0.73, p < 0.05).
conclusionThe glucuronidation of OHM appears immature in preterm infants less than 2 weeks of age. The observed increase in urinary excretion of OHMG with postconceptional age likely reflects the combined maturation of glucuronidation and renal function.
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