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Carol L Lilly and Barbara Kaplan-Machlis

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OBJECTIVE: To review the literature on the proposed mechanisms of teratogenicity of older antiepileptic drugs (AEDs) compared with lamotrigine.

DATA SOURCES: Published articles on the use of AEDs during pregnancy were identified from a comprehensive MEDLINE search of the English-language literature (January 1966–January 1998). Additional articles were selected from the references. Search terms included antiepileptic drugs, lamotrigine, and pregnancy.

STUDY SELECTION: Only human clinical and pharmacokinetic trials and case studies performed in Europe and the US were included.

DATA SYNTHESIS: Pharmacologic characteristics of the older AEDs that appear to contribute to teratogenicity include antifolate effects, metabolism to oxide metabolites, induction of the hepatic cytochrome P450 system, and a high degree of protein binding. The pharmacokinetics and pharmacodynamics of lamotrigine may offer advantages over other AEDs in terms of teratogenicity because lamotrigine is metabolized by the glucuronidation pathway and is not known to induce the hepatic cytochrome P450 system or to form oxide metabolites. The protein-binding capacity of lamotrigine is considerably lower than that of older AEDs, and antifolate effects have not been observed in humans.

CONCLUSIONS: Although few data are available, lamotrigine appears to have pharmacokinetic and pharmacodynamic properties that suggest a safer outcome with its use in pregnancy compared with older AEDs.

J Pharm Technol 1999;15:75-8.

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