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 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.
Scriba
G K
GK
Department of Pharmaceutical Chemistry, School of Pharmacy, University of Münster, Germany.
Lambert
D M
DM
Poupaert
J H
JH
D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D005989:Glycerides / Q000494:pharmacology*; D008297:Male; D010672:Phenytoin / Q000737:chemistry / Q000493:pharmacokinetics*; D011355:Prodrugs / Q000737:chemistry / Q000493:pharmacokinetics*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D005989:Glycerides; D011355:Prodrugs; D010672:Phenytoin