Bioavailability and Anticonvulsant Activity of a Monoglyceride-derived Prodrug of Phenytoin After Oral-administration To Rats

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 of C-max and 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 1 h after dosing the monoglyceride compared to 2 h 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.