Giroux M, Teixera M G, Dumas J C, Desprats R, Grandjean H, Houin G
INSERM CJF 9406, CHU La Grave, France.
Biol Neonate. 1997;72(3):133-41. doi: 10.1159/000244476.
The placental transfer of three opioids used in peridural analgesia, fentanyl, alfentanil and sufentanil, and two reference substances, antipyrine and *H2O, was determined ex vivo in the human placental cotyledon system. (1) In the first set of experiments, the infusion rates were constant and fixed at physiological flow rates. Under these conditions, the magnitude of the materno-fetal transfer was in the following order: *H2O = antipyrine = fentanyl > alfentanil > sufentanil. No particular influence of molecular weight, lipophilia, pKa or the degree of ionization could be discerned. (2) In the second set of experiments, the influence of different flow rates, reflecting various pathophysiological conditions, was examined. There was a linear relationship between the maternal flow and the materno-fetal transfer of the three opioids. On the other hand, for antipyrine and tritiated water, the relationship was logarithmic, a difference attributed to the marked lipophilia of the opioids. (3) At high maternal flow rates, saturation was observed for all five substances due to the short duration of contact with the membrane. There were logarithmic relationships between the maternal flow and the materno-fetal transfer. (4) These findings emphasize the importance of the lipophilic and hydrophilic characteristics of drugs on placental transfer, especially in the event of fluctuations in maternal flow.
在人胎盘小叶系统中通过体外实验测定了用于硬膜外镇痛的三种阿片类药物（芬太尼、阿芬太尼和舒芬太尼）以及两种参比物质（安替比林和*H₂O）的胎盘转运情况。（1）在第一组实验中，输注速率恒定并固定在生理流速。在这些条件下，母胎转运的程度顺序如下：*H₂O = 安替比林 = 芬太尼 > 阿芬太尼 > 舒芬太尼。未发现分子量、亲脂性、pKa或电离程度有特别影响。（2）在第二组实验中，研究了反映各种病理生理状况的不同流速的影响。三种阿片类药物的母体流速与母胎转运之间存在线性关系。另一方面，对于安替比林和氚标记水，这种关系是对数关系，这种差异归因于阿片类药物显著的亲脂性。（3）在高母体流速下，由于与膜接触时间短，所有五种物质均观察到饱和现象。母体流速与母胎转运之间存在对数关系。（4）这些发现强调了药物的亲脂性和亲水性特征对胎盘转运的重要性，尤其是在母体流速波动的情况下。
