Effect of Carbamazepine on Pharmacokinetics of Valproic acid at Steady State

Aim To observe the effects of oral Carbamazpine(CBZ) on serum concentrations at steady state and its pharmacokinetics of Valproic acid(VPA) in New Zealand rabbits.Methods The experiment was divided into 2 stages.(Ⅰ)The rabbits only received a four-day course of oral VPA until steady state.(Ⅱ)VPA combined with CBZ seven days.The dose of VPA is 30mg·kg -1 ·d -1 and the dose of CBZ is 40mg·kg -1 ·d -1 for rabbits.The serum concentration of VPA was determined by FPIA.The two series of pharmacokinetics parameters were analysed by statistic method.Results There was significant increasing of VPA blood concentration at peak value time(0.5 and 1.0h) in Ⅱ stage (P0.01,P0.05).The VPA blood concentration hadn't statistic meaning at the others time though they had change.The eliminate(T 1/2β )of VPA in Ⅱ stage was notable lower than that of Ⅰstage.The other pharmacokinetics parameters were not changed significantly between two stages.Conclusion The Cmax of VPA was notabale increased and its T 1/2 was shortened in Ⅱ stage.It is necessary monitored the blood concentration of VPA and changed the therapeutic dose of VPA when it is taken with CBZ.