Effect of Wuling powder on the pharmacokinetics of valproic acid in epileptic rats

Purpose: To investigate the effect of Wuling powder (WP) on the pharmacokinetics of valproic acid (VPA) in epileptic rats. Methods: A model of epilepsy was established in SD rats by intraperitoneal injection of pentylenetetrazole (PTZ). Twelve epileptic rats were randomly divided into two groups: control group given oral VPA alone at a dose of 180 mg/kg VPA, and drug combination group orally given VPA (180 mg/kg) co-administered with WP at a dose of 200 mg/kg. Blood sample (0.5 mL) was collected at 15, 30, 60, 120, 240 and 720 min after drug administration for measurement of plasma concentrations of VPA using ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Results: The AUC (0-480min) and maximum plasma concentrations (C-max) of VPA in the drug combination group were significantly higher than those in the control group (p < 0.01). The half-time (t(1)(/2)) and time taken to attain maximum plasma VPA concentration (T-max) in the combination group were extended, when compared to control group (p < 0.05). Conclusion: These results demonstrate that WP increases the plasma concentration of VPA and affects the pharmacokinetic properties of VPA in epileptic rats. Thus, the pharmacodynamic influence of this interaction should be taken into consideration while prescribing WP to epileptic patients already taking VPA.