Pharmacometric Evaluation of Umbilical Cord Blood Concentration-Based Early Initiation of Treatment in Methadone-Exposed Preterm Neonates
In methadone-exposed preterm neonates, early identification of those at risk of severe neonatal abstinence syndrome (NAS) and use of a methadone dosing regimen that can provide effective and safe drug exposure are two important aspects of optimal care. To this end, we reviewed 17 methadone dosing re...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-02-01
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| Series: | Children |
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| Online Access: | https://www.mdpi.com/2227-9067/8/3/174 |
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| author | Samira Samiee-Zafarghandy Tamara van Donge Karel Allegaert John van den Anker |
| author_facet | Samira Samiee-Zafarghandy Tamara van Donge Karel Allegaert John van den Anker |
| author_sort | Samira Samiee-Zafarghandy |
| collection | DOAJ |
| description | In methadone-exposed preterm neonates, early identification of those at risk of severe neonatal abstinence syndrome (NAS) and use of a methadone dosing regimen that can provide effective and safe drug exposure are two important aspects of optimal care. To this end, we reviewed 17 methadone dosing recommendations in the international guidelines and literature and explored their variability in key dosing strategies. We selected three of the reviewed dosing regimens for their pharmacokinetics (PK) characteristics and their exposure–response relationship in three gestational age groups of preterm neonates (28, 32 and 36 gestational age weeks) at risk for development of severe NAS (defined as an umbilical cord methadone concentration of ≤60 ng/mL, following fetal exposure). We applied early (12 h after birth) vs. typical (36 h after birth) initiation of treatment. We observed that use of universally recommended dosing regimens in preterm neonates can result in under- or over-exposure. Use of a PK-guided dosing regimen resulted in effective target exposures within 24 h after birth with early initiation of treatment (12 h after birth). Future prospective studies should explore the incorporation of umbilical cord methadone concentrations for early identification of preterm neonates at risk of developing severe NAS and investigate the use of a PK-guided methadone dosing regimen, so that treatment failure, prolonged length of stay and opioid over-exposure can be avoided. |
| first_indexed | 2024-03-09T00:33:19Z |
| format | Article |
| id | doaj.art-41aa7611c22f416f8f79fdb4eada2b96 |
| institution | Directory Open Access Journal |
| issn | 2227-9067 |
| language | English |
| last_indexed | 2024-03-09T00:33:19Z |
| publishDate | 2021-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Children |
| spelling | doaj.art-41aa7611c22f416f8f79fdb4eada2b962023-12-11T18:19:09ZengMDPI AGChildren2227-90672021-02-018317410.3390/children8030174Pharmacometric Evaluation of Umbilical Cord Blood Concentration-Based Early Initiation of Treatment in Methadone-Exposed Preterm NeonatesSamira Samiee-Zafarghandy0Tamara van Donge1Karel Allegaert2John van den Anker3Division of Neonatology, Department of Paediatrics, McMaster University, Hamilton, ON L8S 4L8, CanadaDivision of Pediatric Pharmacology and Pharmacometrics, University Children’s Hospital Basel (UKBB), University of Basel, 4056 Basel, SwitzerlandDepartment of Clinical Pharmacy, Erasmus MC, Postbus 2040, 3000 CA Rotterdam, The NetherlandsDivision of Pediatric Pharmacology and Pharmacometrics, University Children’s Hospital Basel (UKBB), University of Basel, 4056 Basel, SwitzerlandIn methadone-exposed preterm neonates, early identification of those at risk of severe neonatal abstinence syndrome (NAS) and use of a methadone dosing regimen that can provide effective and safe drug exposure are two important aspects of optimal care. To this end, we reviewed 17 methadone dosing recommendations in the international guidelines and literature and explored their variability in key dosing strategies. We selected three of the reviewed dosing regimens for their pharmacokinetics (PK) characteristics and their exposure–response relationship in three gestational age groups of preterm neonates (28, 32 and 36 gestational age weeks) at risk for development of severe NAS (defined as an umbilical cord methadone concentration of ≤60 ng/mL, following fetal exposure). We applied early (12 h after birth) vs. typical (36 h after birth) initiation of treatment. We observed that use of universally recommended dosing regimens in preterm neonates can result in under- or over-exposure. Use of a PK-guided dosing regimen resulted in effective target exposures within 24 h after birth with early initiation of treatment (12 h after birth). Future prospective studies should explore the incorporation of umbilical cord methadone concentrations for early identification of preterm neonates at risk of developing severe NAS and investigate the use of a PK-guided methadone dosing regimen, so that treatment failure, prolonged length of stay and opioid over-exposure can be avoided.https://www.mdpi.com/2227-9067/8/3/174preterm neonatemethadoneneonatal abstinence syndromedosing |
| spellingShingle | Samira Samiee-Zafarghandy Tamara van Donge Karel Allegaert John van den Anker Pharmacometric Evaluation of Umbilical Cord Blood Concentration-Based Early Initiation of Treatment in Methadone-Exposed Preterm Neonates Children preterm neonate methadone neonatal abstinence syndrome dosing |
| title | Pharmacometric Evaluation of Umbilical Cord Blood Concentration-Based Early Initiation of Treatment in Methadone-Exposed Preterm Neonates |
| title_full | Pharmacometric Evaluation of Umbilical Cord Blood Concentration-Based Early Initiation of Treatment in Methadone-Exposed Preterm Neonates |
| title_fullStr | Pharmacometric Evaluation of Umbilical Cord Blood Concentration-Based Early Initiation of Treatment in Methadone-Exposed Preterm Neonates |
| title_full_unstemmed | Pharmacometric Evaluation of Umbilical Cord Blood Concentration-Based Early Initiation of Treatment in Methadone-Exposed Preterm Neonates |
| title_short | Pharmacometric Evaluation of Umbilical Cord Blood Concentration-Based Early Initiation of Treatment in Methadone-Exposed Preterm Neonates |
| title_sort | pharmacometric evaluation of umbilical cord blood concentration based early initiation of treatment in methadone exposed preterm neonates |
| topic | preterm neonate methadone neonatal abstinence syndrome dosing |
| url | https://www.mdpi.com/2227-9067/8/3/174 |
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