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Human brain, plasma, and cerebrospinal fluid concentration of sodium valproate after 72 hours of therapy

From the Department of Neurology (Drs. Vajda, Donnan, and Bladin) and Clinical Pharmacology (Dr. Vajda and Ms. Phillips), University of Melbourne, Austin Hospital, Heidelberg, Australia.

Addreas correspondence and reprint requests to Dr. Vajda, Department of Neurology, Austin Hospital, Heidelberg, Victoria 3084, Australia.

Nine neurosurgical patients suffering from a variety of brain tumors were studied. Sodium valproate was given for 3 days before surgery. At craniotomy, sections of brain and samples of cerebrospinal fluid (CSF) and plasma were obtained and assayed for sodium valproate concentrations. Brain levels were 6.8 to 27.9% of plasma concentrations, and CSF levels were 7.6 to 25.0% of plasma levels. There was a significant correlation between brain and CSF levels and plasma on Spearman ranking. These results confirm that valproate is not selectively concentrated in brain fractions, and the concentration in brain is related to the free anticonvulsant level in plasma.

Acknowledgments We wish to thank Mr. J. Calvert, F.R.A.C.S., and Mr. J. Woodward, F.R.A.C.S., for their help with this project.

Accepted for publication June 13, 1980.