Thomas Jefferson University Philadelphia, Pennsylvania, United States
Background: Ondansetron is a 5-HT3 receptor antagonist that has been used as an antiemetic but has utility in treating neonatal opioid withdrawal syndrome (NOWS). A Bayesian model was developed to describe ondansetron pharmacokinetics (PK) in pregnant women and neonates. Methods: Sparse PK data were analyzed from a multicenter, double blind clinical trial (NCT 01965704) with 98 opioid-dependent, otherwise healthy pregnant women and 90 neonates. Pregnant women were randomized to receive either placebo or ondansetron 8 mg intravenously (IV) within 4 hours of delivery. Neonates born to mothers who were randomized to ondansetron received ondansetron 0.07 mg/kg orally or 0.04 mg/kg IV once every 24 hours for up to 5 doses. Using two published PK models, ondansetron PK parameters were estimated with NONMEM software via Bayesian estimation. Results: A two-compartmental model was constructed to describe ondansetron PK separately in pregnant women and neonates. Since there was insufficient data collected to describe the absorption phase after oral dosing in neonates, the overall model was insensitive to changes in the absorption rate constant (ka) as confirmed by changes in objective function value via a sensitivity analysis. This was fixed to 0.5 assuming the time to maximal concentration is 1.5 hours. The point estimates for volume of distribution (V) and clearance (CL) as well as 90% confidence intervals (CI) for pregnant women and neonates are provided in the Table. Conclusion: The established model reasonably describes ondansetron PK in pregnant women and neonates. The model may be used to identify an optimized dose for the treatment of NOWS in neonates.
