Effect of Timing on the Administration of Spherical Charcoal (Kremezin) on the Pharmacokinetics of Valproic Acid in Rats

The effect of timing on the administration of spherical charcoal (Kremezin) on the pharmacokinetics of valproic acid (VPA) in the coadministration of sodium valproate and Kremezin was examined in rats.Kremezin, when administered either immediately or 30 min after the administration of sodium valproate, significantly decreased the area under the plasma concentration-time curve (AUC) 0-3 of VPA by about 30%. In addition, when Kremezin was administered 30 min or 1 hr before sodium valproate dosing it decreased the maximum plasma concentration (Cmax) of VPA by 39% and 27%, respectively, and significantly decreased the AUC0-3 of VPA by 54% and 45%, respectively. The plasma VPA concentrations in all Kremezin-treated groups were significantly lower than those in the controls. However, Kremezin administered 1 hr after sodium valproate dosing had no effect on the plasma VPA concentration, Cmax or AUC0-3 of VPA.These results suggest that Kremezin decreased the absorption of VPA due to adsorption after the coadministration of sodium valproate and Kremezin.