ABSTRACT
Phenacemide (PAC) (phenylacetylurea) was synthesized by Spielman in 1948, used in the early 1950s for all types of epilepsy, and then abandoned in the same decade because of fatalities. PAC metabolism has been extensively studied in the rabbit, where the drug appears to be metabolized by hydroxylation of the benzene nucleus, followed by methylation of the 3 hydroxyl group and by hydrolysis of the ureide group. The aromatic hydroxylation reactions may occur by mechanisms that involve arene oxide metabolites. These intermediates are very reactive and may have substantial toxic potential by virtue of their ability to bind covalently to macromolecules. Serum creatinine has been reported markedly increased in three patients receiving PAC. This abnormality is attributed to the increased conversion of creatine to creatinine and is not indicative of renal disease. Both patients had evidence of progressive anemia from other AEDs before PAC treatment. Fatalities appeared unrelated to the total cumulative dose.
