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Bioavailability of rectally administered valproic acid syrup

Departments of Pharmaceutical Services (Dr Cloyd) and Pediatric Neurology 1Dr. Kriel). St. Paul-Ramsey Medical Center, College of Pharmacy and School of Medicine, University of Minnesota, Minneapolis, MN.

The bioavailability of commercially available valproic acid (VPA) syrup was studied following rectal administration in both dogs and children. Six dogs were studied following both oral (PO) and rectal (PR) administration of a dilute VPA syrup given in a dose of 40 mg per kilogram. There was no significant difference (p >0.1) in the area under the serum concentration-time curve AUC) between the oral (201.1 mg L ₁hr) and rectal (219.6mg L ₁hr) routes of administration. Four children were given VPA syrup by the rectal route. In three patients on maintenance VPA therapy, absorption following rectal administration was similar to that following oral administration. In a fourth child, VPA serum levels following an initial rectal dose of 20 mg per kilogram reached a maximum of 42 mg per liter 2 hours after the drug was given. These results indicate that the bioavailability of a diluted VPA syrup given rectally is comparable to that following oral administration. Rectal administration of VPA syrup appears to be a satisfactory alternative when the oral route is unavailable.

Address correspondence and reprint requests to Dr. Cloyd, Department of Pharmaceutical Services, St. Paul-Ramsey Medical Center, St. Paul, MN 55101.

Accepted for publication January 16, 1981.

Supported in part by grants from St. Paul-Ramsey Medical Center Medical Education and Research Foundation, and Roche Laboratories, Division of Hoffman-LaRoche. Inc.

Presented in part at the ninth annual meeting of the Child Neurology Society. October 2, 1980, Savannah, GA.

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