Bioavailability of rectally administered valproic acid syrup

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 greater than 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.