Dose-adjusted plasma concentrations of sublingual buprenorphine are lower during than after pregnancy.
Dose-adjusted plasma concentrations of sublingual buprenorphine are lower during than after pregnancy.
复制标题
舌下丁丙诺啡的剂量调整后血浆浓度比怀孕后低。
DOI：
10.1016/j.ajog.2016.09.095
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发表时间：
2017-01
影响因子：
9.8
通讯作者：
Caritis SN
中科院分区：
文献类型：
--
作者：
Bastian JR;Chen H;Zhang H;Rothenberger S;Tarter R;English D;Venkataramanan R;Caritis SN
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. This study evaluated the impact of physiological changes associated with pregnancy on the PK of sublingual buprenorphine during and after pregnancy. Pregnant women (N=13), between 18 0/7 and 37 6/7 weeks’ singleton gestation, receiving sublingual buprenorphine twice daily for opioid use disorders were studied. PK-2 studies were performed between 18–25 weeks (N=7), PK-3 studies were performed between 31–37 weeks (N=11), and PK-P was performed 4–18 weeks postpartum (N=10). On the day of study, blood was withdrawn prior to the daily morning dose of buprenorphine and at 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 8 and 12h post-dose. Buprenorphine plasma concentrations were analyzed by LCMS-MS. All PK parameters were observed or estimated using Microsoft Excel. Statistical analyses were performed to identify significant changes in study participants’ buprenorphine pharmacokinetic parameter estimates over the duration of the study. Univariate linear and generalized linear mixed models were employed to investigate changes in these measures over time, some of which were log transformed for normality. Dose-normalized (plasma concentration/dose) buprenorphine plasma concentrations were significantly lower during pregnancy (PK-2 + PK-3) than during the postpartum period (PK-P). Specific PK parameters (and level of significance) were as follows: the area under the BUP plasma concentration-time curves (AUC0→12, p<0.003), maximum BUP concentrations (Cmax, p<0.018), average BUP concentrations (Cavg, p<0.003), BUP concentrations at 0h (C0, p<0.002) and BUP concentrations at 12h (C12, p<0.001). None of these parameters differed significantly during pregnancy (ie PK-2 vs PK-3). The time to maximum BUP concentrations (Tmax) did not differ significantly between groups. The dose-normalized plasma concentrations during a dosing interval and the overall exposure of BUP (AUC0→12) are lower throughout pregnancy compared to the postpartum period. This indicates an increase in apparent clearance of BUP during pregnancy. These data suggest that pregnant women may need a higher dose of sublingual buprenorphine compared to postpartum individuals. The dose of buprenorphine should be assessed after delivery to maintain similar buprenorphine exposure during the postpartum period.
