ABSTRACT
Department of Hospital Pharmacy, Faculty of Medicine, University of the Ryukyus, 207 Uehara, Nishihara-cho, Okinawa 903-0215, Japan Department of Pharmacology, School of Medicine, Faculty of Medicine, University of the Ryukyus, 207 Uehara, Nishihara-cho, Okinawa 903-0215, Japan
Abstract-Effects of salicylate on the pharmacokinetics of valproic acid (VPA) after oral administration (p.o.) of sodium valproate were investigated in rats. When salicylic acid was administered orally after sodium valproate p.o., the plasma VPA concentrations including maximum plasma concentration (Cmax), area under the plasma concentration-time curve up to 3 h (AUC0-3) and the elimination half-life (/1/2) of VPA were lower than control values. In addition, when salicylate was administered intraperitoneally or intravenously, the plasma VPA concentrations, AUC0-3 and /1/2 of VPA were lower than those in the control group. These results suggest that decreases in the plasma VPA concentrations including Cmax and AUC0-3 with simultaneous oral administration of sodium valproate and salicylic acid may be related to both reduction of absorption and increase in clearance of VPA.
