Trial reportJournal of clinical pharmacology2019
Recently Registered Midazolam Doses for Preterm Neonates Do Not Lead to Equal Exposure: A Population Pharmacokinetic Model.
Trial report in Journal of clinical pharmacology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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
12 citing papers in PubMed.
- A CYP3A7 metabolically competent human induced pluripotent stem cell-derived hepatocyte-like cell (hHLCDrug metabolism and disposition: the biological fate of chemicals · 2026Article
- Pharmacological therapy of neonatal analgosedation: current status, dilemmas, and perspectives.Frontiers in pediatrics · 2026Review
- Midazolam-Induced Seizure-Like Activity in Five Neonates: A case series.Sultan Qaboos University medical journal · 2024Article
- Getting the dose right using physiologically-based pharmacokinetic modeling: dexamethasone to prevent post-extubation stridor in children as proof of concept.Frontiers in pediatrics · 2024Article
- Biomarkers for assessing pain and pain relief in the neonatal intensive care unit.Frontiers in pain research (Lausanne, Switzerland) · 2024Review
- Grading the level of evidence of neonatal pharmacotherapy: midazolam and phenobarbital as examples.Pediatric research · 2024Article
- The Use of Midazolam as an Antiseizure Medication in Neonatal Seizures: Single Center Experience and Literature Review.CNS & neurological disorders drug targets · 2024Observational
- Off-Label, but on-Evidence? A Review of the Level of Evidence for Pediatric Pharmacotherapy.Clinical pharmacology and therapeutics · 2022Review
- Sedation level with midazolam: A pediatric surgery approach.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2022Review
- The bioavailability and maturing clearance of doxapram in preterm infants.Pediatric research · 2021Article
- Cerebral Oxygenation and Activity During Surgical Repair of Neonates With Congenital Diaphragmatic Hernia: A Center Comparison Analysis.Frontiers in pediatrics · 2021Article
- Enantiomer specific pharmacokinetics of ibuprofen in preterm neonates with patent ductus arteriosus.British journal of clinical pharmacology · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Although midazolam is a frequently used sedative in neonatal intensive care units, its use in preterm neonates has been off-label. Recently, a new dosing advice for midazolam for sedation on intensive care units has been included in the label (0.03 mg/[kg·h] for preterm neonates <32 weeks and 0.06 mg/[kg·h] for neonates >32 weeks). Concentration-time data of a prospective multicenter study (29 patients, median gestational age 26.7 [range 24.0-31.1 weeks]) were combined with previously published data (26 patients, median gestational age 28.1 [range 26.3-33.6 weeks]), and a population pharmacokinetic model describing the maturation of midazolam pharmacokinetics was developed in NONMEM 7.3. Clearance was 73.7 mL/h for a neonate weighing 1.1 kg and changed nonlinearly with body weight (exponent 1.69). Volume of distribution increased linearly with body weight and was 1.03 L for a neonate weighing 1.1 kg. Simulations of the newly registered dosing show considerable differences in steady-state concentrations in preterm neonates. To reach similar steady-state concentrations of 400 µg/mL (±100 µg/mL), a dose of 0.03 mg/(kg·h) is adequate for neonates ≥1 kg and ≤2 kg but would have to be reduced to 0.02 mg/(kg·h) (-33%) in neonates <1 kg and increased to 0.04 mg/(kg·h) (+33%) in neonates weighing >2 kg and ≤2.5 kg. The impact of the observed differences in exposure is difficult to assess because no target concentrations have yet been defined for midazolam, but the current analysis shows that one should be cautious in giving dosage advice based on historical data with a lack of reliable pharmacokinetic and effect data.
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Registered trials
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