Background: NAS is a set of physiologic signs of withdrawal resulting from opiate exposure, either in utero or as part of medical care.Although enteral morphine is used to treat NAS, the pharmacokinetics (PK) is unknown.A better understanding of the PK and clinical covariates will allow for future simulations and links to pharmacodynamic (PD) endpoints, allowing for individualized dosing and improved symptom control.The objective of this analysis is to develop a population PK (PopPK) model on interim data, the first on enteral morphine in NAS, which can be used to develop an integrated PKPD model after trial completion.Methods:Infants＞35 weeks gestational age exposed to heroin or methadone in utero, morphine or fentanyl in the ICU,and at risk for treatment or currently being treated with enteral morphine were enrolled.Previously published PopPK model of morphine and its two metabolites, M3G and M6G, after Ⅳ administration was used to fit the observed concentrations from 19 infants with an add-on absorption compartment allowing estimation of bioavailability (BA) of morphine and formation of metabolites using Phoenix NLME V_1.3.(data 11/20/13,analyzed 12/3/13).Results: In accordance with literature, results from this model indicate extensive first pass metabolism, approximately 60％ of enteral morphine in this neonatal population.About 49％ is converted into inactive metabolite, M3G and only 11％ into the active metabolite M6G.Conclusion: The add-on absorption compartment morphine PopPK model fit the interim observed morphine, M3G and M6G concentration data in neonates with NAS well with reasonable parameter estimates.The BA estimated from this model will allow optimized dosing strategy to reduce the duration and exposure to morphine in infants being treated for NAS.