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目的:研究托吡酯(TPM)达稳态时添加单剂量丙戊酸钠(VPA)与单剂量VPA在血清及脑脊液(CSF)中药动学的主要药动学参数的变化,探索TPM达稳态时对单剂量VPA存在的药物相互作用及意义。方法:8只Beagle犬,随机分成2组,采取平行对照。A组给予单剂量VPA;B组给予TPM达稳态后添加单剂量VPA。采用气相色谱-质谱法检测TPM的药物浓度,荧光偏振免疫分析法检测VPA的药物浓度。结果:当TPM达稳态时添加单剂量VPA后,血清中VPA的MRT上升、tmax上升、Cmax下降,差异有显著性(P<0.05),在CSF中VPA的MRT上升t、max上升,差异有显著性(P<0.05),其余参数差异无显著性(P>0.05)。结论:TPM达稳态时添加单剂量VPA后,TPM可加快VPA在血清及CSF中的代谢,降低其药物浓度,可能在临床上具有当两药联合应用时需对剂量进行调整的指导意义。
OBJECTIVE: To study the main pharmacokinetic parameters of topiramate (TPM) in the steady state of TPM and the pharmacokinetic parameters of single-dose VPA and single-dose VPA in serum and cerebrospinal fluid (CSF) Drug interactions and significance of single-dose VPA. Methods: Eight Beagle dogs were randomly divided into two groups, taking parallel control. Group A received a single dose of VPA; Group B received TPM up to a steady state and then received a single dose of VPA. The drug concentration of TPM was detected by gas chromatography-mass spectrometry, and the drug concentration of VPA was detected by fluorescence polarization immunoassay. Results: When TPM reached steady state, the MRT of VPA increased, tmax increased, Cmax decreased, the difference was significant (P <0.05), the MRT of VPA in CSF increased t and max increased, (P <0.05), while the other parameters had no significant difference (P> 0.05). CONCLUSION: TPM up-regulates the metabolism of VPA in serum and CSF and decreases the drug concentration after TPM reaches its steady-state. It is possible that TPM can adjust the dosage when the two drugs are used in combination.