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Valproic acid pharmacokinetics in children. II.

Discontinuation of concomitant antiepileptic drug therapy

From the Department of Pediatric Neurology, St. Paul-Ramsey Medical Center; the Department of Pharmacy Practice, College of Pharmacy and the Comprehensive Epilepsy Program, University of Minnesota, Minneapolis, MN; and the Clinical Pharmacokinetics Laboratory, College of Pharmacy, University of Illinois Medical Center, Chicago, IL.

We studied the pharmacokinetics of valproic acid (VPA) in 11 children before and after discontinuance of enzyme-inducing antiepileptic drugs (AEDs). Valproic acid elimination half-life increased from 7.1 to 11.8 hours. Total and intrinsic VPA clearance decreased by approximately 40%. Valproic acid serum protein binding varied among patients from 7 to 23.8%, but was not altered by AEDs. Seizure control was maintained and mental status improved once all other AEDs were withdrawn. After discontinuation of enzyme-inducing AEDs, serum VPA concentrations can be maintained with a lower VPA dosage given less frequently.

Address correspondence and reprint requests to Dr. Cloyd, University of Minnesota, College of Pharmacy, Health Sciences Unit F, 308 Harvard Street SE, Minneapolis, MN 55455.

Funded in part by grants from the St. Paul-Ramsey Medical Center Medical Education and Research Foundation, Epilepsy Foundation of America, and University of Minnesota College of Pharmacy.

Accepted for publication March 7, 1985.

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