Methadone dosing strategies in preterm neonates can be simplified

British Journal of Clinical Pharmacology
Tamara van DongeJohn van den Anker

Abstract

A 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. A 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. A 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 ...Continue Reading

Associated Clinical Trials

Apr 1, 2011·John van den Anker

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Citations

Oct 14, 2020·Expert Opinion on Drug Metabolism & Toxicology·Matthijs W van HoogdalemTomoyuki Mizuno
Mar 3, 2021·Clinical and Translational Science·Fei TangMarkos Leggas

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