Bioavailability and Anticonvulsant Activity of a Monoglyceride‐Derived Prodrug of Phenytoin after Oral Administration to Rats

Abstract

The plasma levels of phenytoin after oral administration of phenytoin and phenytoin 2‐monoglyceride, a phenytoin prodrug, to rats were determined by gas chromatography. Compared to the application of the parent drug, administration of the prodrug resulted in a 3‐fold increase ofCmaxand a 4‐fold increase of the AUC. This correlated with an earlier onset and peaking of the anticonvulsant activity determined in the maximal electroshock (MES) test. The peak effect was reached 1h after dosing the monoglyceride compared to 2h after application of phenytoin itself. On the basis of the median effective dose, the prodrug was 3 times more effective antagonizing MES‐induced seizures than the parent drug. It is concluded that phenytoin 2‐monoglyceride might be a useful prodrug for the oral delivery of phenytoin.