Impact of Pregnancy on Buprenorphine Pharmacokinetics and Pharmacodynamics

Currently, the standard of care for an opioid-dependent pregnant woman in most institutions is methadone, however, buprenorphine (BUP) is also used for this indication, as it is FDA-approved for opioid addiction although not specifically for pregnant women. There has been increasing evidence that BUP may have comparable efficacy to methadone, and may have fewer severe neonatal complications especially neonatal abstinence syndrome (NAS) and decreased severity of adverse reactions. The dosing of BUP currently is based on studies in men and non-pregnant women (adjusted to the patient's symptomatology using the Clinical Opiate Withdrawal (COW) score, some of which is subjective and some based on objective physiological parameters) and limited animal data that related plasma concentrations of BUP to the degree of saturation of the µ receptor in the brain. The study team will define the pharmacokinetics and limited pharmacodynamics of BUP in early and late pregnancy and the postpartum period and determine what contributes to the variation in plasma concentrations and response and will also relate plasma concentrations of BUP and its major metabolites to physiologic parameters that can be used to gauge the amount of drug in mother's plasma. It is expected to demonstrate that higher doses of BUP are needed throughout pregnancy and that the dosing regimen can be adjusted using patient covariates and biophysical measurements in addition to the COW scores.