Effects of food on valproic acid absorption

The effect of food on valproic acid absorption was investigated in a randomized, cross-over study with eight subjects. Two 250-mg soft-gelatin capsules of valproic acid were administered to the participants under fasting and nonfasting conditions. The time of peak serum concentration, height of the peak concentration, and total area under the curve were determined and compared by the Student's t test for paired data. The time to attain a peak serum concentration was significantly delayed (p less than 0.005) from the 1.6 hours during fasting conditions to four hours after a standard meal. A statistically insignificant trend toward lower peak serum concentrations (54.6 micrograms/ml versus 49.4 micrograms/ml) was found under the nonfasting conditions. This trend becomes significant if the data of one subject who exercised before taking the drug are eliminated. The area under the curve was not different between the two conditions. The administration of the drug with food did not significantly alter the volume of distribution, half-life, or elimination constant. No clinically important interaction resulted from the administration of valproic acid with food. If a patient experiences gastrointestinal side effects with valproic acid, the patient may be advised to take the drug with food.