Pharmacokinetics and muscle histopathology of intramuscular valproate

To determine the safety and pharmacokinetics of parenteral sodium valproate healthy mature greyhound dogs, were given intramuscular injections following intravenous injections. Dosings intravenously and intramuscularly were at 20, 40 and 60 mg/kg in the three groups. Intravenous infusion rates were constant. Sodium valproate solution concentrations of 300, 400 and 500 mg/ml were administered. Intramuscular valproate was quickly absorbed. Bio-availability approached 70%. Half life of 120 min was calculated. Toxic muscle necrosis was observed at all concentrations. Dosing valproate intramuscularly in humans is problematic in view of the muscle damage. Despite tissue damage sodium valproate was well absorbed intramuscularly. The intravenous injection of valproate at high concentrations, large doses and fast infusion rates produced no evidence of cardiotoxicity and levels of 180 micrograms/ml.