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Intravenous valproate

Effects on plasma and saliva phenytoin levels

From the Institute of Clinical Neurology, University of Messina, Messina, Italy.

Address correspondence and reprint requests to Dr. Pisani, Clinica Neurologica dellUniversita, Policlinico "G. Martino," 98013 Contesse, Messina, Italy.

Plasma and saliva phenytoin was evaluated at fixedtime intervals after intravenous (IV) administration of 800 mg valproate in epileptics chronically treated with phenytoin monotherapy. A significant fall in plasma and a concurrent significant increase of the drug in saliva (which reflects the free amount in plasma) were observed, with maximal changes occurring at 30 to 90 minutes after valproate infusion. Present data indicate that valproic acid is able to displace phenytoin from plasma proteins, suggesting a critical evaluation of the routine phenytoin plasma levels (which reflect free + bound fraction) when this drug is administered concurrently with sodium valproate.

Acknowledgments We are grateful to Dr. Di Rosa, Dr. Fazio, Mr. Forestieri, and Dr. Serra for their assistance. We also wish to thank Sigma-Tau (Pomezia, Italy) for supplying the vials of lyophilized sodium valproate for intravenous use.

Accepted for publication June 19, 1980.