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E600mg／d，另一组空白对照。连续14d，在第15天两组均同时口服辛伐他汀40mg。在0、0．25、0．5、0、75、1、1．5、2、2．5、3、4、6、8、12、24h采5mL外周静脉血，洗脱4周交叉进行下阶段试验。采血后0、5h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Cmax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 metabilism 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 ran： domly 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 at0, 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-a- tocopherol 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 drag interaction occurs between RRR-a-tocopherol and Simvastatin, which can decrease lipid-lowering effect and lead to adverse drug reaction.