Department of Obstetrics and Gynecology, Turku University Central Hospital, Turku, Finland.
Eur J Pharm Sci. 2011 Oct 9;44(3):181-6. doi: 10.1016/j.ejps.2011.07.002. Epub 2011 Jul 12.
Our aim was to investigate the placental transfer of repaglinide by ex vivo placental perfusion experiment. In addition, the involvement of the active organic anion transporters (OATP1B1, OATP1B3 and OATP2B1) was studied by assessing the single nucleotide polymorphisms (SNPs) in genes (SLCO1B1, SLCO1B3 and SLCO2B1) encoding OATPs.
Fifteen placentas were obtained after delivery and a 2-h non-recirculating perfusion of a single placental cotyledon was performed to study maternal-to-fetal and fetal-to-maternal transport of repaglinide by using antipyrine as a reference of passive-diffusion transfer compound. Genotyping was performed for all placentas.
Maternal-to-fetal transfer of repaglinide and antipyrine were 1.5% and 13.2%, respectively, and fetal-to-maternal transfers were 6.7% and 40.3%, respectively. Fetal-to-maternal transfer of repaglinide was statistically significantly higher than maternal-to-fetal transfer (P<0.0001). The number of placentas was not sufficient for proper statistical analysis, but the fetal-to-maternal transfer seemed to be affected by the SLCO1B3 polymorphism.
The placental transfer of repaglinide from mother to fetus was low. Since a higher transfer rate of repaglinide was observed in fetal-to-maternal than maternal-to-fetal direction, active transport by OATP-transporters may be an important factor in fetal exposure to repaglinide.
通过离体胎盘灌注实验研究瑞格列奈的胎盘转运。此外，通过评估编码 OATP 的基因（SLCO1B1、SLCO1B3 和 SLCO2B1）中的单核苷酸多态性（SNP），研究活性有机阴离子转运体（OATP1B1、OATP1B3 和 OATP2B1）的参与情况。
分娩后获得 15 个胎盘，并对单个胎盘小叶进行 2 小时非再循环灌注，以使用安替比林作为被动扩散转运化合物的参考，研究瑞格列奈的母体向胎儿和胎儿向母体转运。对所有胎盘进行基因分型。
瑞格列奈和安替比林的母体向胎儿转移分别为 1.5%和 13.2%，而胎儿向母体转移分别为 6.7%和 40.3%。瑞格列奈的胎儿向母体转移明显高于母体向胎儿转移（P<0.0001）。由于进行适当的统计分析所需的胎盘数量不足，但胎儿向母体的转移似乎受到 SLCO1B3 多态性的影响。
瑞格列奈从母体向胎儿的胎盘转移率较低。由于在胎儿向母体的转移率高于母体向胎儿的转移率，因此 OATP-转运体的主动转运可能是胎儿暴露于瑞格列奈的重要因素。
