Antimetrazol action and plasma levels of valproate in developing rats

The duration of protective action of valproate (VPA, 400 mg/kg i.p.) against metrazol-induced seizures was studied in rats aged 7, 12, 18 and 90 days. Fifteen, protected. The results differed between the various age groups after longer intervals: The protection was longest in 18-day-old rats--seizures did not appear even six hours after VPA administration. On the contrary, all 7-day-old rat pups exhibited seizures two hours after VPA. Plasma levels of VPA were measured by means of gas chromatography in the same age groups after an identical dose of VPA. After a single injection of VPA a clear-cut two-peak curve of plasma level was found in all young groups, which may be due to an enterohepatic recirculation of VPA. The maximum plasma levels were lowest in 7-day-old rats, the three older groups exhibited similar values. Plasma half-life was longest in the youngest animals (9.24) and decreased with age; values for 18- and 901 day-old rats did not differ (2.57 and 3.05 h respectively). No clear-cut correlation was found between the antimetrazol action and its plasma levels.