天然维生素E对辛伐他汀体内代谢的影响

目的 阐明天然维生素E 对降脂药辛伐他汀代谢的影响。 方法 12 名男性健康志愿者, 随机分两组, 采用两阶段双周期交叉设计。一组口服天然维生素E 600 mg d, 另一组空白对照。连续14 d, 在第15 天两组均同时口服辛伐他汀40 mg 。在0 、0.25 、0.5 、0.75、1 、1.5、2、2.5、3 、4 、6 、8 、12 、24 h 采5 mL 外周静脉血, 洗脱4 周交叉进行下阶段试验。采血后0.5 h 内进行离心和分离血浆, 运用HPLC-MS-MS 分别测定血浆中辛伐他汀总药物浓度、辛伐他汀酸药物浓度, 分析比较不同处理组间药代动力学参数的差异。 结果 天然维生素E 服用组辛伐他汀、辛伐他汀酸血浆药物浓度显著降低。天然维生素E 服用组与空白对照组之间辛伐他汀曲线下面积AUC_(0~24h) 和峰浓度Cmax 之间的差异有统计学意义(P <0.05) 。天然维生素E 服用组与空白对照组辛伐他汀酸曲线下面积AUC_(0~24h) 和峰浓度C_max 之间的差异也有统计学意义(P <0.05) 。 结论 天然维生素E明显加快了辛伐他汀的清除速度, 辛伐他汀与天然维生素E 同时服用有可能产生药物相互作用,降低其降脂效果, 导致不良反应。

Effects of regular consumption of RRR-a-tocopherol on the metabolism of simvastatin

AIM: RRR-a-tocopherol is an essential micronutrient which can activate the pregnane X receptor (PXR) and regulate the expression of its target gene CYP3A and P-glycoprotein.Simvastatin is metabolized and transported by CYP3A and P-glycoprotein.The aims of the study was to investigate the effect of RRR-a-tocopherol on the metabolism of Simvastatin in vivo. METHODS: In a two-stage doubly periodic cross-over study, 12 healthy volunteers, who were randomly divided into two groups, ingested RRR-a-tocopherol 600 mg or placebo(control) for 14 days.On the fifteenth day, a single 40 mg dose of Simvastatin was taken by all of them and 5 mL peripheral vein blood of each one was taken at 0, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5,3, 4, 6, 8, 12 and 24 h.The plasma concentrations of Simvastatin and Simvastatin-acid were determined by HPLC-MS-MS after centrifugation and blood plasma separation.The differences of pharmacokinetic parameters of every control groups were compared and analyzed. RESULTS: The plasma concentrations of Simvastatin and Simvastatin-acid of RRR-atocopherol group decreased obviously.Both the area under the curve of AUC(0 ~ 24h) of Simvastatin of RRR-a-tocopherol group and control group and Cmax of each showed significant difference (P <0.05);The area under the curve of AUC(0~24h) and Cmax of Simvastatinacid also showed an obvious difference between the two groups (P <0.05). CONCLUSION: RRR-a-tocopherol can significantly induce the clearance rate of Simvastatin.Great attention should be paid when the drug interaction occurs between RRR-a-tocopherol and Simvastatin, which can decrease lipid-lowering effect and lead to adverse drug reaction.