The Use of Methadone in Newborn Infants

• Status: Completed
• Trial end date: 2017-12-01
• Target enrollment: 0
• Participant gender: All

Summary

This proposed investigation will test the following hypotheses: 1) Enzymatic activity of CYP2B6 characterized by the formation clearance of methadone to EDDP (CLf,EDDP), is directly related to both gestational and postnatal age; 2) variations in the CYP2B6 gene (SNPs) are associated with variable activity of the CYP2B6 enzyme (as measured by the formation clearance, CLf,EDDP), and 3) the elimination rate of methadone and its major metabolite EDDP in neonates is dependent on the glomerular filtration rate and therefore on the stage of development (defined by both gestational and postnatal age). The investigators propose to develop a PK model for methadone dosing in neonates that takes into account both developmental stage and genetic variability. The long-term goal of the proposed investigations is to improve dosing of methadone in neonates exposed to opioids in utero or post-natally, leading to improved control of their withdrawal syndrome and decreased adverse drug reactions associated with the current use of methadone in these vulnerable patients. More immediately, the investigators will develop a PK model for methadone dosing based on relevant developmental and genetic characteristics. The acquired knowledge based on the proposed study will lead to a more efficacious treatment of pain or opiate withdrawal syndrome in newborn infants with a decreased chance of adverse drug reactions.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: John van den Anker
• Treatments: Fentanyl; Methadone; Morphine; Pharmaceutical Solutions

Criteria

Inclusion Criteria:

• Newborn infants of both genders and all races who have:

• a postnatal age of less than 3 months

• an indwelling (peripheral or umbilical) arterial line, and

• already treated with an opioid (morphine or fentanyl) for clinical reasons

Exclusion Criteria:

• Neonates with severe asphyxia grade III or IV intraventricular hemorrhage,

• Neonates with major congenital malformations or facial malformations (e.g., cleft lip and palate), neurological disorders

• Neonates receiving continuous or intermittent neuromuscular blockers neonates will be excluded who have:

• clinical or biochemical evidence of hepatic and renal failure (including systemic hypoperfusion

• received drugs that are CYP2B6 substrates

• been exposed in utero to methadone, despite the fact that they indeed receive a CYP2B6 substrate through their mother, will not be excluded but will be analyzed as a subgroup