隐丹参酮单剂量和多剂量给药在大鼠体内药代动力学研究

Pharmacokinetics of Cryptotanshinone with Single and Multiple Doses in Rats

目的评价单剂量和多剂量灌胃隐丹参酮（Cryptotanshinone,CTS）的药动学特征。方法将20只SD雄性大鼠随机分为单剂量组（隐丹参酮10 mg/kg,1 d）、多剂量组（隐丹参酮10 mg/kg,每天1次,连续10 d）给予灌胃后,用LC-MS/MS法测定血浆中隐丹参酮的浓度。血药浓度数据用DAS 2.0药代动力学软件处理,按两室模型拟合并求算药代动力学参数。结果隐丹参酮单剂量给药后,Cmax为（12.16±14.11）ng/m L,Tmax为（2.88±2.56）h,T1/2为（3.70±3.50）h,MRT为（6.69±0.54）h,AUC0～24为（58.40±25.73）ng·h/m L;多剂量给药后,Cav为（1.95±0.61）ng/m L,Tmax为（3.20±2.08）h,T1/2为（7.12±5.06）h,AUCss为（46.74±14.51）ng·h/m L,DF为2.42±0.28。单剂量和多剂量的AUC0～24、Tmax、T1/2差异无统计学意义。结论隐丹参酮长期给药后无蓄积风险。

Objective To evaluate the pharmacokinetic properties of cryptotanshinone （CTS） with single and multiple doses administration in SD rats. Methods Totally 20 male SD rats were randomly divided into 2 groups： the single-dose group （CTS 10 mg/kg, 1 d） and multiple-dose group （CTS 10 mg/kg, once a day, 10 consecutive days）. The CTS concentration in plasma was detected by LC-MS/MS method. The data of plasma concentration was processed by DAS 2.0 software and the pharmaeokinetic parameters were calculated according to a two-compartment open model. Results The pharmacokinetic parameters obtained from the single-dose study were as follows： Cmax was （12.16±14.11） ng/mL, Tmax was （2.88±2.56） h, T1/2 was （3.70±3.50） h, MRT was （6.69±0.54） h and AUC0-24 was （58.40±25.73） ng.h/mL; The pharmacokinetic parameters obtained from the multiple-dose study were as follows： Cav was （1.95±0.61） ng/mL, Tmax was （3.20±2.08） h, T1/2 was （7.12±5.06） h, AUC was （46.74±14.51） ng-h/mL and DF was 2.42±0.28. There was no significant difference in AUC0-24, Tmax and T1/2 of single and multiple doses. Conclusion There was no risk of accumulation after long-term administration with cryptotanshinone.