Fokina Valentina M, West Holly, Oncken Cheryl, Clark Shannon M, Ahmed Mahmoud S, Hankins Gary D V, Nanovskaya Tatiana N
Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, TX.
Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, TX.
Am J Obstet Gynecol. 2016 Oct;215(4):497.e1-7. doi: 10.1016/j.ajog.2016.05.016. Epub 2016 May 12.
Bupropion is used for treatment of depression during pregnancy. However, its use as a smoking cessation aid for pregnant women is currently under evaluation.
The aim of this opportunistic study was to investigate the transfer of bupropion and its major pharmacologically active metabolites, hydroxybupropion and threohydrobupropion, across the placenta in vivo. In addition, the concentrations of the drug and its metabolites were determined in the amniotic fluid.
The following samples were collected at deliveries from 22 women taking bupropion: maternal blood (n = 22), umbilical cord venous blood (n = 22), and amniotic fluid (n = 9). The concentrations of the drug and its metabolites in blood plasma and amniotic fluid were determined by means of liquid chromatography-mass spectrometry. Placental passage was calculated as a ratio of umbilical cord venous plasma to maternal plasma concentrations.
The levels of hydroxybupropion and threohydrobupropion in umbilical cord venous plasma were invariably lower than their corresponding concentrations in maternal plasma. The concentrations of bupropion in umbilical cord plasma were lower than in maternal plasma in the majority of the maternal-cord blood pairs. The median values of the umbilical cord venous plasma to maternal plasma ratios were: bupropion, 0.53 (interquartile range 0.35, n = 18), hydroxybupropion, 0.21 (interquartile range 0.12, n = 18), and threohydrobupropion, 0.61 (interquartile range 0.11, n = 21). In umbilical cord venous plasma, the median concentration of bupropion was 5.3 ng/mL; hydroxybupropion, 103.6 ng/mL; and threohydrobupropion, 59.6 ng/mL. Bupropion and its metabolites were detectable in the amniotic fluid but the concentrations of threohydrobupropion were higher than those in the corresponding umbilical cord venous plasma.
Bupropion and its active metabolites cross the placenta to the fetal circulation. The concentrations of hydroxybupropion and threohydrobupropion in umbilical cord venous plasma were higher than bupropion concentrations suggesting a higher fetal exposure to the metabolites than the parent drug. The higher levels of threohydrobupropion in the amniotic fluid than those in umbilical cord venous plasma suggest that enzymes involved in the metabolism of bupropion to threohydrobupropion are most likely active in the fetus. The biological consequences of fetal exposure to maternally administered bupropion and/or its active metabolites via placental transfer and recirculation of the amniotic fluid are yet to be determined.
安非他酮用于孕期抑郁症的治疗。然而，其作为孕妇戒烟辅助药物的用途目前正在评估中。
这项机会性研究的目的是在体内研究安非他酮及其主要药理活性代谢物羟基安非他酮和苏式羟基安非他酮通过胎盘的转运情况。此外，还测定了羊水中药物及其代谢物的浓度。
从22名服用安非他酮的妇女分娩时采集以下样本：母体血液（n = 22）、脐静脉血（n = 22）和羊水（n = 9）。采用液相色谱-质谱法测定血浆和羊水中药物及其代谢物的浓度。胎盘通过率通过脐静脉血浆与母体血浆浓度之比计算得出。
脐静脉血浆中羟基安非他酮和苏式羟基安非他酮的水平始终低于母体血浆中的相应浓度。在大多数母血-脐血对中，脐血浆中安非他酮的浓度低于母体血浆。脐静脉血浆与母体血浆浓度之比的中位数为：安非他酮0.53（四分位间距0.35，n = 18），羟基安非他酮0.21（四分位间距0.12，n = 18），苏式羟基安非他酮0.61（四分位间距0.11，n = 21）。在脐静脉血浆中，安非他酮的中位数浓度为5.3 ng/mL；羟基安非他酮为103.6 ng/mL；苏式羟基安非他酮为59.6 ng/mL。羊水中可检测到安非他酮及其代谢物，但苏式羟基安非他酮的浓度高于相应脐静脉血浆中的浓度。
安非他酮及其活性代谢物可通过胎盘进入胎儿循环。脐静脉血浆中羟基安非他酮和苏式羟基安非他酮的浓度高于安非他酮浓度，表明胎儿对代谢物的暴露高于母体药物。羊水中苏式羟基安非他酮的水平高于脐静脉血浆中的水平，这表明参与安非他酮代谢为苏式羟基安非他酮的酶很可能在胎儿体内具有活性。胎儿通过胎盘转运和羊水再循环暴露于母体给予的安非他酮和/或其活性代谢物的生物学后果尚待确定。
