Utilizing Pediatric Physiologically Based Pharmacokinetic Models to Examine Factors That Contribute to Methadone Pharmacokinetic Variability in Neonatal Abstinence Syndrome Patients
| Autor: | Chie Emoto, Jason R. Wiles, Brooks T. McPhail, Henry T. Akinbi, Alexander A. Vinks, Dawn Butler, Tsuyoshi Fukuda |
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| Rok vydání: | 2019 |
| Předmět: |
Pharmacology
business.industry medicine.disease 030226 pharmacology & pharmacy 03 medical and health sciences Drug withdrawal 0302 clinical medicine Neonatal abstinence Opioid Pharmacokinetics In utero 030220 oncology & carcinogenesis medicine Pharmacology (medical) business Intrauterine exposure Pharmacogenetics medicine.drug Methadone |
| Zdroj: | The Journal of Clinical Pharmacology. 60:453-465 |
| ISSN: | 1552-4604 0091-2700 |
| DOI: | 10.1002/jcph.1538 |
| Popis: | Chronic intrauterine exposure to psychoactive drugs often results in neonatal abstinence syndrome (NAS). NAS is the symptomatic drug withdrawal in newborns that generally occurs after in utero chronic opioid exposure. Methadone is an opioid analgesic commonly prescribed for pharmacologic management of NAS. It exhibits high pharmacokinetic (PK) variability. The current study used physiologically based PK modeling to predict the PK profile of methadone in 20 newborns treated for NAS. The physiologically based PK simulations adequately predicted the PK profile of the clinical data for 45% of the patients. Sensitivity analyses were conducted to explore contributing factors to methadone PK variability. The data suggest that P450 enzymatic activity impacts the clearance of methadone in virtual adults and neonates, while the contribution of cardiac output may be negligible. Understanding maturational and/or pharmacogenetic changes in cytochrome P450 enzymatic activity may further explain the large PK variability of methadone in newborns with NAS and will help individualized treatment. |
| Databáze: | OpenAIRE |
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