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