Background and objective: In addition to the standard antiepileptic drugs, traditional Chinese medicines (TCMs) are used for the treatment of epilepsy in oriental countries. The interactions between antiepileptic drugs and TCMs represent a potential problem in clinical application. Because valproic acid (VPA), one of the most widely prescribed antiepileptic drugs, may be administered concomitantly with Paeoniae Radix (PR), one of the famous TCMs, in some epileptic patients, the present study was conducted to evaluate the influences of PR on the pharmacokinetics of VPA.
Method: The pharmacokinetics of VPA were investigated in a randomized, open-label, two-way crossover study. Six healthy volunteers received the following treatments in a crossover design: (i) 1·2 g extract powder of Paeoniae Radix once daily for 7 days and one 200 mg VPA gastro-resistant tablet on day 7 and (ii) one 200 mg VPA gastro-resistant tablet alone on day 7. Serial plasma samples were obtained on day 7. Total and free (unbound) VPA plasma concentrations were determined by fluorescence polarization immunoassay (FPIA). Safety measures included laboratory tests (haematology, serum chemistry and urinalysis) and adverse event monitoring. Statistical comparisons of pharmacokinetic parameters were performed with the Student paired t-test.
Results: Overall clinical safety was satisfactory. The mean maximum plasma concentration of VPA was attained at within 6 h after oral administration of VPA alone and 3–4 h after oral administration of VPA in combination with PR. The plasma level of VPA declined with a half-life of 11·71 and 11·91 h, respectively. No statistically significant difference was obtained in any of the pharmacokinetic parameters (Tmax, Cmax, AUC, t1/2, MRT, CL/F and Vd/F) of VPA between the two treatments. Also, there was no significant difference in the protein binding rates of VPA.
Conclusion: PR did not significantly affect the absorption, distribution, metabolism and elimination of VPA in healthy volunteers.