Phenytoin-lipid conjugates as potential prodrugs of phenytoin.

Phenytoin-1-triglycerides and phenytoin-2-triglycerides were synthesized as potential prodrugs of phenytoin by covalent binding of 3-hydroxymethylphenytoin by succinic acid to the positions 1 and 2 of diglycerides, respectively. The corresponding 1- and 2-monoglycerides were prepared. In addition, replacement of glycerol by 3-hydroxy-2-hydroxymethylpropionic acid furnished lipids that allowed direct coupling of 3-hydroxymethylphenytoin. The lipid conjugates proved to be substrates for pancreatic lipase in vitro.