Infant outcome after prenatal exposure to antiepileptic compounds is of considerable concern to women with epilepsy. Under most circumstances it would be detrimental to both mother and fetus to have the medication withdrawn during pregnancy.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 (e.g., growth problems and postnatal developmental delays) is of considerable importance. Carbamazepine (CBZ Tegretol""""""""), the current drug of choice in temporal lobe epilepsy, is used as an alternative to phenytoin (PHT Dilantin""""""""), which is known to induce teratogenicity. Although little is known about the actual mechanism of CBZ teratogenicity, oxidative metabolism has been implicated. Oxcarbazepine (OCBZ Trileptol""""""""), an experimental compound in the U.S. (currently in clinical use in Europe), seems to be as efficacious as CBZ and is more easily tolerated by patients. OCBZ is metabolized via reduction to form a monohydro x y derivative, whereas CBZ is oxidized to form an epoxide. This difference avoids the formation of reactive arene oxides and epoxides possibly responsible for the teratogenicity of CBZ. However, the potential liability of OCBZ to prenatally exposed infants is not known. The goal of this research project is to test the teratogenicity of OCBZ in a monkey model. Breeding females are brought to steady-state efficacious plasma levels of CBZ or OCBZ and then bred concurrently with control females that have not received either drug. When the infants are born, they are transferred to the Infant Primate Research Laboratory, where growth parameters, motor development, and cognitive development are monitored. The number of cycles to conception in the OCBZ females has been more than twice that of the control and CBZ females, but the pregnancies have resulted in viable infants. Developmental and cognitive data from the infants are now being analyzed. FUNDING NIH grants RR00166 and NS37177. Lockard, J.S., Congdon, W.C., Burkhead-Potter, T., and Phillips, N.K. Oxcarbazepine single and multiple-dose kinetics in monkey induction and intrinsic inhibition? Epilepsia 39 (suppl. 6) 48, 1998.
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