Pharmacokinetics of Oral Methadone in the Treatment of Neonatal Abstinence Syndrome: A Pilot Study.
J Pediatr
; 167(6): 1214-20.e3, 2015 Dec.
Article
em En
| MEDLINE
| ID: mdl-26364984
ABSTRACT
OBJECTIVE:
To characterize the population pharmacokinetics of oral methadone in neonates requiring pharmacologic treatment of neonatal abstinence syndrome and to develop a pharmacokinetic (PK) model toward an evidence-based treatment protocol. STUDYDESIGN:
Based on a methadone dosing protocol, serum concentrations of methadone and its metabolites were assessed by high performance liquid chromatography-tandem mass spectrometry from dried blood spots. Population PK analysis was performed to determine the volume of distribution and clearance of oral methadone. Methadone plasma concentration-time profiles were simulated from the deduced PK model to optimize the dosing regimen.RESULTS:
There was substantial interindividual variability in methadone concentrations. Blood concentrations of methadone were best described by a 1-compartment model with first-order absorption. The population mean estimates (coefficient of variation percentage) for oral clearance and volume of distribution were 8.94 (103%) L/h/70 kg and 177 (133%) L/70 kg, respectively. Optimized dosing strategies were developed based on the simulated PK profiles. We suggest a starting dose of 0.1 mg/kg per dose every 6 hours for most patients requiring pharmacologic treatment of neonatal abstinence syndrome followed by an expedited weaning phase.CONCLUSIONS:
The proposed dosing regimen may reduce the cumulative dose of opioid and shorten the length of hospitalization. Future studies should aim to validate the simulated dosing schemes with clinical data and expand our understanding of the between-patient PK variability. TRIAL REGISTRATION ClinicalTrials.gov NCT01754324.
Texto completo:
1
Coleções:
01-internacional
Contexto em Saúde:
2_ODS3
/
8_ODS3_consumo_sustancias_psicoactivas
Base de dados:
MEDLINE
Assunto principal:
Síndrome de Abstinência Neonatal
/
Analgésicos Opioides
/
Metadona
Tipo de estudo:
Guideline
Limite:
Humans
/
Newborn
Idioma:
En
Revista:
J Pediatr
Ano de publicação:
2015
Tipo de documento:
Article