Valproic acid effects on leukocytes and platelets of Sprague-Dawley rats

A study with valproic acid (VPA) was performed in Sprague-Dawley rats with the aim of relating drug serum levels to variations of leukocytes, platelets, coagulation time and other haematological parameters. VPA, 20 and 240 mg/kg, were administered orally, three times a day in groups of rats of both sexes throughout 7, 14, 30, 60 and 90 day periods. Total blood leukocytes averaged 7296 +/- 443 in control as well as in treated groups. Lymphocytes and monocytes decreased in all five groups when receiving the TD50 of 240 mg/kg (P less than 0.05). The VPA fasting serum levels were detectable if administered at 8 hr intervals. Nevertheless, VPA caused modification of the chosen parameters. VPA t1/2 averaged 3 hr in rats. Thus, even if the VPA effects were observed in our experiments, we suggest dividing the whole VPA dose into eight portions to be administered at 3 hr intervals in rats to attain constant serum VPA levels as well as constant drug effects.