| Summary: | 博士 === 台北醫學院 === 藥學研究所 === 89 === Except for the standard antiepileptic drugs, traditional Chinese medicines (TCM) are used for the treatment of epilepsy in oriental countries. We previously reported that many patients (16.32 %) used or had used TCM for the treatment of epilepsy even when scientific medicine has been provided. Therefore, the interactions between antiepileptic drugs and TCM represent a potential problem for the treatment of epilepsy. Interactions between TCM and antiepileptic drugs may increase or decrease the pharmacological or toxicological effects of either component, however, lack of report about the pharmacokinetic interactions between antiepileptic drugs and TCM. Since Paeoniae Radix (PR) is one of the TCM used as an adjuvant agent in some epileptic patients and may be administered concomitantly with antiepileptic drugs in clinical situations, the present study was conducted to evaluate the influences of PR on the pharmacokinetics and protein binding of the widely prescribed antiepileptic drugs, phenytoin (PHT), carbamazepine (CBZ) and valproic acid (VPA).
A single dose of test drug alone or in combination with PR extract was administered, respectively. The serial blood samples were obtained and measured by high-performance liquid-chromatography (HPLC). The free (unbound) plasma concentrations were determined by fluorescence polarization immunoassay (FPIA). The plasma concentrations were used to construct pharmacokinetic profiles by plotting drug concentration-time curves. All data were subsequently processed by the computer program WINNONLIN (SCI, Lexington).
In the study results, the mean maximum plasma concentration of PHT was attained at within 2 h after oral administration of PHT alone and 4-6 h after oral administration of PHT in combination with PR. The plasma level of PHT declined with a half-life of 5.38 and 4.03 h, respectively. No statistically significant differences were obtained in most of pharmacokinetic parameters (Cmax, AUC, T1/2, MRT and CL/F) and protein binding rates of PHT between the two treatments, however, the significant differences in Tmax and Vd/F between groups were noted.
In addition, the mean maximum plasma concentration of CBZ was attained at 1-4 h after oral administration of CBZ alone and within 2 h after oral administration of CBZ in combination with PR. The significant decrease in Tmax of CBZ was noted when CBZ was combined with PR. The plasma level of CBZ declined with a half-life of 8.60 and 7.69 h, respectively. There were no significant differences in Cmax, AUC, T1/2, MRT, CL/F and Vd/F of CBZ between the two groups. A significant decrease in protein binding rate was found while CBZ was co-administered with PR. Further studies are in progress to clarify the clinical significance and the mechanism underlying the effects of PR on the protein binding of CBZ.
Finally, 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 all 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
The pharmacokinetic interaction between antiepileptic drugs and PR are revealed to anticipate the efficacy and to reduce the risk of antiepileptic drugs in clinical applications.
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