Phenytoin prodrugs

SA Varia, S Schuller, KB Sloan, VJ Stella. Phenytoin prodrugs III Water-soluble prodrugs for oral and/or parenteral use. J Pharm Sci 73(8) 1068-1073, 1984. 

Y Yumiko, RD Roberts, VJ Stella. Low-melting phenytoin prodrugs as alternative oral delivery modes for phenytoin A model for other high-melting sparingly water-soluble drugs. J Pharm Sci 72(4) 400-405, 1983. 

Fosphenytoin, the water-soluble phosphate ester of phenytoin, is a phenytoin prodrug. 

Y. Yamaoka, R. D. Roberts, J. V. Stella, Low-Melting Phenytoin Prodrugs as Alternative Oral Delivery Modes for Phenytoin A Model for Other High-Melting Sparingly Water-Soluble Drugs , J. Pharm. Sci. 1983, 72, 400 - 405. 

V. J. Stella, S. Martodihardjo, V. M. Rao, Aqueous Solubility and Dissolution Rate Does not Adequately Predict in vivo Performance A Probe Utilizing Some N-Acyloxymethyl Phenytoin Prodrugs , J. Pharm. Sci. 1999, 88, 775 - 779. 

S. A. Varia, S. Schuller, K. B. Sloan, V. J. Stella, Phenytoin Prodrugs III Water-Soluble Prodrugs for Oral and/or Parenteral Use , J. Pharm. Sci. 1984, 73, 1068- 1073 S. A. Varia, S. Schuller, V. J. Stella, Phenytoin Prodrugs IV Hydrolysis of Various 3-(Hy-droxymethyl)phenytoin Esters , J. Pharm. Sci. 1984, 73, 1074-1080 S. A. Varia, V. J. Stella, Phenytoin Prodrugs V In vivo Evaluation of Some Water-Soluble Phenytoin Prodrugs in Dogs , J. Pharm. Sci. 1984, 73, 1080-1087. 

G. K. E. Scriba, D. M. Lambert, J. H. Poupaert, Anticonvulsant Activity of Phenytoin-Lipid Conjugates, a New Class of Phenytoin Prodrugs , J. Pharm. Pharmacol. 1995, 47, 197-203. 

S. A. Varia, V. J. Stella, Phenytoin Prodrugs VI In vivo Evaluation of a Phosphate Ester Prodrug of Phenytoin after Parenteral Administration to Rats , J. Pharm. Sci. 1984, 73, 1087-1090. 

Varia, S., S. Schuller, K. B. Sloan, and V. J. Stella. 1984a. Phenytoin prodrugs. III. VWter-soluble prodrugs for oral and/or parenteral usA. Pharm. Sci73 1068-1073. 

Varia, S.A., and V.J. Stella. 1984. Phenytoin prodrugs V In vivo evaluation of some water-soluble phenytoin prodrugs in dogs. J Pharm Sci 73 1080. 

Prodrugs that are more lipophilic than the parent drug can increase membrane pentration and thus oral drag absorption. Thus it was shown that phenytoin 2-monoglyceride, a lipophilic phenytoin prodrug, afforded a 4-fold increase in oral bioavailability in the rat. 

Intravenous phenytoin has been associated with fatal hemodynamic complications and serious reactions at the injection site, including skin necrosis and amputation of extremities. Fosphenytoin, a phenytoin prodrug, has the same pharmacological properties but none of the injection site and cardiac rhythm complications after intravenous administration (64). 

CL Dougherty, J Kres, H Davoudi. Bio availability studies of drugs with nonlinear pharmacokinetics. II. absolute bioavailability of intravenous phenytoin prodrug at therapeutic phenytoin serum concentrations determined by doublestable isotope technique. J Clin Pharmacol 33 89-94, 1993. 

Varia, A.A. and Stella, V.J. (1984) Phenytoin prodrugs. VI In vivo evaluation of a phosphate ester prodrug of phenytoin after parenteral administration to rats. /. Pharm. ScL 73 1087-1090. 

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