Protein binding of four antiepileptic drugs in maternal and umbilical cord serum.
The total and protein free levels of 4 antiepileptic drugs (AEDs) in serum from 35 maternity patients who had been treated with AED monotherapy throughout pregnancy were studied. Results were compared with those in the umbilical cord serum at the time of delivery, and the placental transfer of AEDs was evaluated from the viewpoint of the protein binding capacity of the drug. The materials consisted of 35 samples of maternal and umbilical cord serum in total and included 13 patients on phenobarbital (PB), 7 on phenytoin (PHT), 7 on carbamazepine (CBZ) and 8 on valproic acid (VPA). The mean fetal/maternal total concentration ratios were 0.86, 0.91, 0.73 and 1.59 for PB, PHT, CBZ and VPA, respectively, only the VPA ratio being above 1. On the other hand, the mean fetal/maternal free fraction ratios were 1.13, 1.10, 1.42 and 0.50 for PB, PHT, CBZ and VPA, respectively, only the VPA ratio being less than 1. Correlation of the 2 ratios showed a reciprocal proportion with a correlation coefficient of -0.90 (P < 0.005). It was considered that the fetal/maternal total concentration ratio of 4 AEDs was regulated by the fetal/maternal free fraction ratio of the corresponding AEDs and that the difference in fetal/maternal free fraction ratio depended on the type of drug being administered.
Takeda
A
A
Department of Internal Medicine, Nagoya National Hospital, Japan.
Okada
H
H
Tanaka
H
H
Izumi
M
M
Ishikawa
S
S
Noro
T
T
D000927:Anticonvulsants / Q000097:blood* / Q000627:therapeutic use; D001798:Blood Proteins / Q000378:metabolism*; D004827:Epilepsy / Q000097:blood* / Q000188:drug therapy; D005260:Female; D005312:Fetal Blood / Q000378:metabolism*; D016231:Fluorescence Polarization Immunoassay; D006801:Humans; D011247:Pregnancy; D011248:Pregnancy Complications / Q000097:blood* / Q000188:drug therapy; D011485:Protein Binding
D000927:Anticonvulsants; D001798:Blood Proteins