1: J Pharm Pharmacol 1995 Nov;47(11):945-8
Bioavailability of phenytoin following oral administration of phenytoin-lipid
conjugates to rats.
Scriba GK, Lambert DM, Poupaert JH
Department of Pharmaceutical Chemistry, University of Munster, Germany.
The bioavailability of phenytoin was evaluated in rats upon oral administration
of phenytoin-lipid conjugates obtained by covalent binding of 3-hydroxymethylphenytoin
to 1,3-dimyristoylglyceride via a succinidyl linkage, to 2-(1,3-dimyristoyl-2-glyceryl)butyric
acid and to 3-myristoyloxy-2-methylpropionic acid. Despite differences
of the phenytoin plasma concentrations all three compounds approximately
doubled the AUC compared with the dosing of phenytoin itself. The early
onset and the long duration of the anticonvulsant activity after administration
of the triglyceride-derived conjugate could be correlated to the increased
phenytoin plasma levels. It is concluded that drug-lipid conjugates may
be useful prodrugs for the oral delivery of poorly water-soluble drugs.
PMID: 8708990, UI: 96286649