ABSTRACT
In the mid-1960s, initial clinical trials with sodium valproate (VPA) were conducted in Europe, and the drug was introduced as a new antiepileptic drug in France in 1967. VPA has been used in all European countries under various trade names and became available in the United States in 1978. Enteric coated preparations have a slower pattern of absorption; these products were developed to avoid local gastric irritation resulting from the transformation of sodium VPA into free acid. The most convincing studies documenting VPA as a teratogen are those of Elizabeth Robert linking the occurrence of spina bifida with the use of VPA. Appropriate liver function studies for patients without hepatotoxicity are serum glutamic oxalacetic transaminase, serum glutamic pyruvate transaminase, lactic dehydrogenase, and gamma-glutamyl transferase. Other congenital abnormalities such as cleft palate, renal agenesis, and facial dysmorphism have been linked with VPA used in combination with other antiepileptic drugs.
