Application of Hollow Type Suppository to Pharmaceutical Preparation in Hospital I. Valproic Acid Suppository.

The evaluation of valproic acid (VPA) hollow type suppository was carried out by a comparison between rectal and oral administration of VPA in 3 healthy volunteers and 10 patients. The oral dosage form was used as tablet or syrup of sodium valproate (VPA-Na) and a hollow type suppository containing VPA in the form of oily liquid was used for the rectal administration. A single oral dose of VPA-Na 7mg/kg or a single rectal dose of VPA 6.02mg/kg was administered to 3 healthy volunteers by a cross over study, respectively. The peak serum concentration (Cmax;45.24±4.84μg/ml) was reached within 1.7 hours after oral administration, while it was reached at 3.09 hours in the case of rectal administration (Cmax;41.28±1.21μg/ml). The areas under the curve of serum concentration (AUC) after oral and rectal administration were 887.76±182.03μg·h/ml and 1021.14±200.70μg·h/ml, respectively. Therefore, relative bioavailability (AUC rectal/AUC oral×100) was 115%. In patients after neurosurgical operation, relative bioavailability was over 88%.These data suggested that VPA was efficiently absorbed from the human rectum after the administration of hollow type suppository.Thus, it was concluded that VPA hollow type suppository could be useful for prophylaxis and management of seizure, especially for the patients who were not able to ingest the oral preparations.