Caritis Steve N, Venkataramanan Raman
From the Departments of Obstetrics and Gynecology and Reproductive Sciences (SNC), Pathology (RV), and Pharmaceutical Sciences (RV), University of Pittsburgh Schools of Medicine and Pharmacy, Pittsburgh, PA.
J Addict Med. 2025;19(2):129-134. doi: 10.1097/ADM.0000000000001380. Epub 2024 Sep 2.
The dosing regimen in the package insert for sublingual buprenorphine is similar for pregnant and nonpregnant people despite the physiologic changes seen during pregnancy.
To compare plasma buprenorphine pharmacokinetics during and after pregnancy and relate buprenorphine concentration to the pharmacodynamic endpoints of pupil diameter, Clinical Opioid Withdrawal Scale (COWS), and craving scores.
Prospective cohort of 22 pregnant people undergoing 33 pharmacologic studies (6-8 hours each) during pregnancy or postpartum. Participants were on a stable daily dose of 2-8 mg sublingual buprenorphine every 6 or 8 hours. The dosing frequency was selected by the participant. On study day, baseline measurements of plasma buprenorphine, pupil diameter, COWS, and craving scores were obtained, then the usual morning dose was taken, and measurements were repeated several times over 1 dosing interval.
The dose-normalized area under the plasma buprenorphine concentration time curve was significantly ( P = 0.036) lower during pregnancy (155 ± 52 ng × min/mL) than postpartum (218 ± 113 ng × min/mL). Buprenorphine trough concentrations were similar at the start (1.1 ± 0.7 ng/mL) and end of a dosing cycle (1.2 ± 0.8 ng/mL) regardless of dosing frequency. Pupillary diameter, COWS, and craving scores returned to baseline as buprenorphine concentrations approached ~1 ng/mL.
Pregnant people require a higher dose of buprenorphine to achieve concentrations comparable to nonpregnant people. There is a temporal relationship between the plasma buprenorphine concentration and the pharmacodynamic markers of pupillary diameter, COWS, and craving scores. An average plasma concentration of ~1 ng/mL was associated with the lowest level of COWS and craving scores.
尽管孕期会出现生理变化，但舌下含服丁丙诺啡包装说明书中的给药方案对孕妇和非孕妇是相似的。
比较孕期和产后血浆丁丙诺啡的药代动力学，并将丁丙诺啡浓度与瞳孔直径、临床阿片戒断量表（COWS）和渴求评分等药效学终点相关联。
对22名孕妇进行前瞻性队列研究，她们在孕期或产后接受了33项药理学研究（每项6 - 8小时）。参与者每天稳定服用2 - 8毫克舌下含服丁丙诺啡，每6或8小时一次。给药频率由参与者选择。在研究日，获取血浆丁丙诺啡、瞳孔直径、COWS和渴求评分的基线测量值，然后服用常规晨剂量，并在1个给药间隔内多次重复测量。
孕期血浆丁丙诺啡浓度 - 时间曲线下剂量标准化面积（155±52纳克×分钟/毫升）显著低于产后（218±113纳克×分钟/毫升）（P = 0.036）。无论给药频率如何，丁丙诺啡谷浓度在给药周期开始时（1.1±0.7纳克/毫升）和结束时（1.2±0.8纳克/毫升）相似。随着丁丙诺啡浓度接近约1纳克/毫升，瞳孔直径、COWS和渴求评分恢复到基线水平。
孕妇需要更高剂量的丁丙诺啡才能达到与非孕妇相当的浓度。血浆丁丙诺啡浓度与瞳孔直径、COWS和渴求评分等药效学标志物之间存在时间关系。平均血浆浓度约1纳克/毫升与最低水平的COWS和渴求评分相关。
