Dose-adjusted Plasma Concentrations of Sublingual Buprenorphine are Lower During than After Pregnancy

Abstract

Background-Buprenorphine is an FDA-approved maintenance therapy for opioid use disorders and is increasingly being used in pregnant women with opioid use disorders as an alternative to methadone. Dosing of buprenorphine in pregnant women is based on the regimen recommended for non-pregnant females and males. Limited data are available defining the pharmacokinetic (PK) properties of sublingual (SL) buprenorphine administered during pregnancy.

Adherence trajectories of buprenorphine therapy among pregnant women in a large state Medicaid program in the United States

“…In addition, late initiators (regardless of their adherence levels) and early initiators with early discontinuation had more inpatient visits and a lower mean buprenorphine daily dose during pregnancy. Given an increase in apparent clearance of buprenorphine during pregnancy, dose escalation of buprenorphine is suggested . Clinicians may consider split dosing in patients complaining of discomfort and craving in the afternoon/evening to prevent relapse .…”

Gestational changes in buprenorphine exposure: A physiologically‐based pharmacokinetic analysis

“…BUP exposure during the postpartum period was simulated in virtual female healthy subjects using SimCyp population simulator. The simulated BUP exposure during 2 nd and 3 rd trimesters and the postpartum period were validated using the observed plasma concentrations of BUP from a prospective clinical BUP PK study in pregnant women during pregnancy (2 nd and 3 rd trimesters) and the postpartum state conducted by our group . In this clinical study, pregnant women with a singleton gestation who were on a stable twice‐daily dose of SL BUP for opioid maintenance therapy for at least 7 days in the 2nd and 3rd trimesters and the postpartum period were evaluated.…”

“…Each woman participated at least in two PK studies; once during the postpartum period and once during the second or third trimesters of pregnancy or in both trimesters. At each study visit, a total of 10 blood samples were collected from 0 h (prior to the morning dose) up to 12 h after the dose and BUP plasma concentrations in these blood samples were measured using high‐performance liquid chromatography with tandem mass spectrometric detection . Our goal was to use the SL BUP pregnancy PBPK model to predict the AUC during pregnancy, and to compare it to the observed data.…”

“…This concentration is associated with 50–60% occupancy of the μ‐opioid receptors in the brain . We have demonstrated in a small cohort of pregnant women that plasma concentrations of BUP and the corresponding BUP exposure is significantly reduced during pregnancy compared to the postpartum state . We have suggested that more frequent dosing of buprenorphine will reduce the time that treated women are likely to be subtherapeutic during pregnancy .…”

“…A better understanding of BUP exposure in pregnancy is required to optimize treatment outcomes in pregnant women with opiate addiction . In our published pilot study, we did not enrol subjects prior to 20 weeks and therefore we were not able to evaluate the changes in BUP pharmacokinetics during the first half of pregnancy .…”