1: J Pharm Sci 1995 Mar;84(3):300-2
Bioavailability and anticonvulsant activity of a monoglyceride-derived prodrug of phenytoin after oral administration to rats.

Scriba GK, Lambert DM, Poupaert JH

Department of Pharmaceutical Chemistry, School of Pharmacy, University of Munster, Germany.

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 Cmax and a 4-fold increase of the AUC. This correlated with an earlier onset and peaking of the anticonvulsant activity determined in the maximal electroschock (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.

PMID: 7616367, UI: 95341463