ArticleBritish journal of clinical pharmacology2019
Methadone dosing strategies in preterm neonates can be simplified.
Article in British 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 8 papers.
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Who cites it
8 citing papers in PubMed, 15 citations in OpenAlex.
- Visceral Pain in Preterm Infants with Necrotizing Enterocolitis: Underlying Mechanisms and Implications for Treatment.Paediatric drugs · 2025Review
- Computing optimal drug dosing with OptiDose: implementation in NONMEM.Journal of pharmacokinetics and pharmacodynamics · 2023Article
- Evaluation of machine learning methods for covariate data imputation in pharmacometrics.CPT: pharmacometrics & systems pharmacology · 2022Article
- A genetic-based population PK/PD modeling of methadone in Chinese opiate dependence patients.European journal of clinical pharmacology · 2022Article
- Leveraging Predictive Pharmacometrics-Based Algorithms to Enhance Perinatal Care-Application to Neonatal Jaundice.Frontiers in pharmacology · 2022Article
- Clinical pharmacology and dosing regimen optimization of neonatal opioid withdrawal syndrome treatments.Clinical and translational science · 2021Review
- Pharmacometric Evaluation of Umbilical Cord Blood Concentration-Based Early Initiation of Treatment in Methadone-Exposed Preterm Neonates.Children (Basel, Switzerland) · 2021Article
- Methadone dosing strategies in preterm neonates can be simplified.British journal of clinical pharmacology · 2019Article
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Authors and funding
7 authors at 4 institutions in 5 countries.
Funding
Abstract
aimsA dramatic increase in newborn infants with neonatal abstinence syndrome has been observed and these neonates are frequently treated with complex methadone dosing schemes to control their withdrawal symptoms. Despite its abundant use, hardly any data on the pharmacokinetics (PK) of methadone is available in preterm neonates. Therefore we investigated developmental PK of methadone and evaluated current dosing strategies and possible simplification in this vulnerable population.
methodsA single-centre open-label prospective study was performed to collect PK data after a single oral dose of methadone in preterm neonates. A population PK model was built to characterize developmental PK of (R)- and (S)-methadone. Model-based simulations were performed to identify a simplified dosing strategy to reach and maintain target methadone exposure.
resultsA total of 121 methadone concentrations were collected from 31 preterm neonates. A one-compartment model with first order absorption and elimination kinetics best described PK data for (R)- and (S)-methadone. Clearance increases with advancing gestational age and differs between R- and S-enantiomer, being slightly higher for the former (0.244 vs 0.167 L/h). Preterm neonates reached target exposure after 48 hours with currently used dosing schedules. Output from simulations revealed that target exposures can be achieved with a simplified dosing strategy during the first 4 days of treatment.
conclusionMethadone clearance in preterm neonates increases with advancing gestational age and its disposition is influenced by its chirality. Simulations that account for developmental PK changes indicate a shorter methadone dosing strategy can maintain target exposure to control withdrawal symptoms.
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