水飞蓟素对辛伐他汀及其活性代谢物在大鼠体内药代动力学的影响。
Effects of Silymarin on the In Vivo Pharmacokinetics of Simvastatin and Its Active Metabolite in Rats.
机构信息
National Clinical Drug Monitoring Center, Department of Pharmacy, Hebei Province General Center, Shijiazhuang 050051, China.
出版信息
Molecules. 2019 Apr 28;24(9):1666. doi: 10.3390/molecules24091666.
Herein, the effect of silymarin pretreatment on the pharmacokinetics of simvastatin in rats was evaluated. To ensure the accuracy of the results, a rapid and sensitive UPLC-MS/MS method was established for simultaneous quantification of simvastatin (SV) and its active metabolite simvastatin acid (SVA). This method was applied for studying the pharmacokinetic interactions in rats after oral co-administration of silymarin (45 mg/kg) and different concentrations of SV. The major pharmacokinetic parameters, including Cmax, tmax, t, mean residence time (MRT), elimination rate constant (λz) and area under the concentration-time curve (AUC), were calculated using the non-compartmental model. The results showed that the co-administration of silymarin and SV significantly increased the Cmax and AUC of SVA compared with SV alone, while there was no significant difference with regards to Tmax and t. However, SV pharmacokinetic parameters were not significantly affected by silymarin pretreatment. Therefore, these changes indicated that drug-drug interactions may occur after co-administration of silymarin and SV.
在此，评估了水飞蓟素预处理对大鼠辛伐他汀药代动力学的影响。为了确保结果的准确性，建立了一种快速灵敏的 UPLC-MS/MS 方法，用于同时定量检测辛伐他汀（SV）及其活性代谢物辛伐他汀酸（SVA）。该方法用于研究大鼠口服水飞蓟素（45mg/kg）和不同浓度 SV 后药代动力学相互作用。使用非房室模型计算主要药代动力学参数，包括 Cmax、tmax、t、平均驻留时间（MRT）、消除速率常数（λz）和浓度-时间曲线下面积（AUC）。结果表明，与单独使用 SV 相比，水飞蓟素和 SV 联合给药显著增加了 SVA 的 Cmax 和 AUC，而 Tmax 和 t 没有显著差异。然而，SV 的药代动力学参数不受水飞蓟素预处理的显著影响。因此，这些变化表明水飞蓟素和 SV 联合给药后可能发生药物相互作用。
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