Pienimäki P, Hartikainen A L, Arvela P, Partanen T, Herva R, Pelkonen O, Vähäkangas K
Department of Pharmacology and Toxicology, University of Oulu, Finland.
Epilepsia. 1995 Mar;36(3):241-8. doi: 10.1111/j.1528-1157.1995.tb00991.x.
Placental transfer and metabolism of carbamazepine (CBZ) was studied in a dual recirculating placental cotyledon perfusion system and was also evaluated in 16 pairs of maternal venous and cord blood samples. Among the parameters studied as possible indicators of a successful perfusion, volume changes in perfusate divided the perfusions into two groups, whereas no significant differences between perfusions were noted in blood gas analysis or in antipyrine transfer. CBZ added into the maternal circulation crosses the placenta in the beginning quicker than antipyrine which is in agreement with the different lipid solubilities of these compounds. Because the transfer rates of antipyrine and CBZ were about the same, the mechanism of transfer of CBZ is probably similar to that of antipyrine (passive diffusion). No metabolites of CBZ could be detected in the perfusate by high-performance liquid chromatography (HPLC) or gas chromatography/mass spectrometry. With the improved HPLC methodology for CBZ metabolites, six metabolites were detected in clinical samples, including 10-hydroxy-10,11-dihydro-CBZ (10-OH-CBZ), which has been described earlier in only 1 uremic patient. Relative levels of metabolites showed significant individual differences. CBZ crosses perfused placenta rapidly, but this does not contribute to CBZ metabolites detected in maternal and fetal circulation.
在双循环胎盘小叶灌注系统中研究了卡马西平（CBZ）的胎盘转运和代谢，并在16对母血静脉血和脐血样本中进行了评估。在作为成功灌注可能指标研究的参数中，灌注液体积变化将灌注分为两组，而在血气分析或安替比林转运方面，各灌注之间未观察到显著差异。添加到母体循环中的CBZ开始时穿过胎盘的速度比安替比林快，这与这些化合物不同的脂溶性一致。由于安替比林和CBZ的转运速率大致相同，CBZ的转运机制可能与安替比林相似（被动扩散）。通过高效液相色谱（HPLC）或气相色谱/质谱法在灌注液中未检测到CBZ的代谢产物。采用改进的HPLC方法检测CBZ代谢产物，在临床样本中检测到6种代谢产物，包括10-羟基-10,11-二氢-CBZ（10-OH-CBZ），此前仅在1例尿毒症患者中描述过。代谢产物的相对水平显示出显著的个体差异。CBZ可迅速穿过灌注的胎盘，但这对母血和胎儿循环中检测到的CBZ代谢产物没有影响。
