Infant outcome after prenatal exposure to antiepileptic compounds is of considerable concern to women with epilepsy. Under most circumstances it would be detrimental to the woman's health, and perhaps that of the fetus, to have the medication withdrawn during pregnancy. At the same time, there is risk to the fetus exposed to antiepileptic compounds and minimizing teratogenicity is crucial. Carbamazepine (CBZ: Tegretol) is the drug choice in temperol lobe epilepsy and has been used as an alternative to phenytoin-induced teratogenesis. Although little is known about the actual mechanism of CBZ teratogenicity, oxidative metabolism has been implicated. Oxcarbazepine (OCBZ: Trileptal), an experimental compound in the U.S. (currently in clinical trials), seems to have equivalent efficacy to CBZ. It has been suggested as a substitute for CBZ due to its greater tolerability by patients. OCBZ is metabolized via reduction (to form a monohydroxy derivative : MHD) as compared to oxidation (CBZ). This difference results in avoidance of arene oxidee intermediaries and reactive epoxides. OCBZ thus has fewer side effects than does CBZ. However, the potential liability of OCBZ to prenatally exposed infants is completely unknown. The goal of the proposed research is to test, in a monkey model, the teratogenicity (e.g., growth problems and postnatal developmental delays) of oxcarbazepine as compared to CBZ. Comparisons will be made among several groups of infants prenatally exposed to : 1) efficacious levels of OCBZ (hydroxylative metabolism) versus carbamazepine (oxidative metabolism) and 2) matched plasma drug levels of synthesized CBZ 10, 11 - epoxide (CBZE: ongoing NIH grant) versus metabolized CBZE (via parental CBZ).

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
1R01NS037177-01
Application #
2466987
Study Section
Neurological Sciences Subcommittee 1 (NLS)
Program Officer
Jacobs, Margaret
Project Start
1997-05-01
Project End
2000-04-30
Budget Start
1997-05-01
Budget End
1998-04-30
Support Year
1
Fiscal Year
1997
Total Cost
Indirect Cost
Name
University of Washington
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
135646524
City
Seattle
State
WA
Country
United States
Zip Code
98195