Nanovskaya Tatiana N, Bowen Robin S, Patrikeeva Svetlana L, Hankins Gary D V, Ahmed Mahmoud S
Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, Texas 77555-0587, USA.
J Matern Fetal Neonatal Med. 2009 Aug;22(8):646-53. doi: 10.1080/14767050802610328.
The aim of this investigation is to determine the effect of human serum albumin (HSA) and alpha-acid glycoprotein (AAG) on buprenorphine (BUP) transplacental transfer and distribution.
The technique of dual perfusion of placental lobule (DPPL) was utilised. BUP was co-perfused with the marker compound antipyrine (AP). In each experiment, the radiolabelled isotopes [(3)H]-BUP and [(14)C]-AP were added to enhance their detection limits. Human plasma proteins, HSA and AAG, were added to both the maternal and fetal circuits separately and in combination at their physiological concentrations in maternal and fetal circulations close to term.
Transplacental transfer of BUP, in absence of plasma proteins, is a two-step process: the first is its uptake by the syncytiotrophoblast from the maternal circuit, and the second is its transfer/release from the tissue to the fetal circuit. The addition of HSA to the perfusion medium affected only the second step of BUP transfer, but AAG affected both steps. The combined effect of HSA and AAG was not different from that observed in presence of the latter alone.
Binding of BUP to circulating AAG could have an important role in the transfer of the drug from the maternal to fetal circulation.
本研究旨在确定人血清白蛋白(HSA)和α-酸性糖蛋白(AAG)对丁丙诺啡(BUP)经胎盘转运和分布的影响。
采用胎盘小叶双灌注技术(DPPL)。将BUP与标记化合物安替比林(AP)共同灌注。在每个实验中,加入放射性标记同位素[³H]-BUP和[¹⁴C]-AP以提高其检测限。将人血浆蛋白HSA和AAG分别以接近足月时母体和胎儿循环中的生理浓度单独或联合添加到母体和胎儿循环回路中。
在无血浆蛋白的情况下,BUP经胎盘转运是一个两步过程:第一步是合体滋养层从母体循环中摄取BUP,第二步是其从组织向胎儿循环的转运/释放。向灌注培养基中添加HSA仅影响BUP转运的第二步,但AAG影响两个步骤。HSA和AAG的联合作用与单独存在AAG时观察到的作用无差异。
BUP与循环中的AAG结合可能在药物从母体循环向胎儿循环的转运中起重要作用。