Abstract: 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.

Key words: RRR-a-tocopherol, Simvastatin, pregnane X receptor