Investigation of low levels of plasma valproic acid concentration following simultaneous administration of sodium valproate and rizatriptan benzoate

Abstract

Drug interaction between rizatriptan benzoate, an anti-migraine agent, and sodium valproate (VPA-Na), an anticonvulsant, was studied in rats. When rizatriptan benzoate was administered orally immediately after VPA-Na oral administration, the pharmacokinetic parameters, such as plasma valproic acid (VPA) and area under the plasma concentration-time curve up to 3 h (AUC(0-3)), were significantly decreased compared with those in the control group. However, when rizatriptan benzoate was administered intraperitoneally immediately after VPA-Na orally, these parameters were not changed. In addition, when benzoic acid was administered orally immediately after VPA-Na orally, these were significantly lower compared with the control values. Therefore, it might be possible that VPA transport by monocarboxylate transporter was competitively inhibited by rizatriptan benzoate and thus absorption of VPA was decreased.

Effects of a dopamine receptor agonist and atropine sulfate on absorption of valproic acid in rats

“…An unexpected change in valproic acid (VPA) concentration after VPA-Na administration might be caused by some co-administered drugs (9,16). In addition, we reported that salicylate (15) and rizatriptan benzoate (8) affected plasma VPA concentration in rats. Therefore, many clinical situations may need reliable therapeutic drug monitoring of VPA for the appropriate dose because of unpredictable drug-interactions.…”