Transplacental passage of oxcarbazepine and its metabolites in vivo.
OBJECTIVE
The purpose of this study was to investigate human fetal exposure to oxcarbazepine (OCBZ) in vivo.


METHODS
Transplacental passage and placental tissue concentrations of OCBZ and its metabolites were determined. Maternal venous blood, cord blood, and placental tissue samples from 12 mothers using OCBZ during pregnancy alone or in combination with other antiepileptic drugs were collected. Samples were analyzed with high-performance liquid chromatography.


RESULTS
Maternal venous concentrations of OCBZ and its major metabolites were at same range as cord blood concentrations (OCBZ in maternal serum, 0.19 +/- 0.16 microg/ml, and in cord serum, 0.21 +/- 0.19 microg/ml; 10-hydroxy-10,11-dihydrocarbamazepine (10-OH-CBZ) in maternal serum, 5.69 +/- 2.49 microg/ml, and in cord serum, 5.23 +/- 1.44 microg/ml; 10,11-trans-dihydroxy-10,11-dihydrocarbamazepine (10,11-D) in maternal serum, 0.29 +/- 0.22 microg/ml, and in cord serum, 0.28 +/- 0.14 microg/ml). OCBZ (0.17 +/- 0.16 microg/g placental tissue), 10-OH-CBZ (3.49 +/- 1.34 microg/g placental tissue) and 10,11-D (0.25 +/- 0.11 microg/g placental tissue) were detected in the placental tissue. The amount of OCBZ detected from placental tissue was 0.01% of the daily dose.


CONCLUSIONS
OCBZ, like other antiepileptic drugs, is transferred significantly through the placenta in humans.
Myllynen
P
P
Department of Pharmacology and Toxicology, University Hospital of Oulu, Oulu, Finland. paivi.k.myllynen@oulu.fi
Pienimäki
P
P
Jouppila
P
P
Vähäkangas
K
K
D000328:Adult; D000927:Anticonvulsants / Q000032:analysis / Q000493:pharmacokinetics* / Q000627:therapeutic use; D002220:Carbamazepine / Q000031:analogs & derivatives* / Q000032:analysis / Q000378:metabolism / Q000493:pharmacokinetics* / Q000627:therapeutic use; D004827:Epilepsy / Q000188:drug therapy / Q000378:metabolism*; D005260:Female; D005312:Fetal Blood / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008431:Maternal-Fetal Exchange / Q000502:physiology; D000078330:Oxcarbazepine; D010920:Placenta / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D011247:Pregnancy; D011248:Pregnancy Complications / Q000188:drug therapy / Q000378:metabolism*
C039775:10,11-dihydro-10-hydroxycarbamazepine; D000927:Anticonvulsants; D002220:Carbamazepine; D000078330:Oxcarbazepine