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.