CARBAMAZEPINE AND ITS METABOLITES IN HUMAN PERFUSED PLACENTA AND IN MATERNAL AND CORD-BLOOD

Placental transfer and metabolism of carbamazepine (CBZ) was studied i n a dual recirculating placental cotyledon perfusion system and was al so evaluated in 16 pairs of maternal venous and cord blood samples. Am ong the parameters studied as possible indicators of a successful perf usion, volume changes in perfusate divided the perfusions into two gro ups, whereas no significant differences between perfusions were noted in blood gas analysis or in antipyrine transfer. CBZ added into the ma ternal 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 simi lar to that of antipyrine (passive diffusion), No metabolites of CBZ c ould be detected in the perfusate by highperformance liquid chromatogr aphy (HPLC) or gas chromatography/mass spectrometry. With the improved HPLC methodology for CBZ metabolites, six metabolites were detected i n 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 c rosses perfused placenta rapidly, but this does not contribute to CBZ metabolites detected in maternal and fetal circulation.