Effects Of Regular Consumption Of RRR-a-tocopherol On The Activity Of CYP3A And P-gp In Vivo

AIMS: Vitamin E is an essential micronutrient involved in various processes relevant to human health and disease. In vitro system RRRa-tocopherol activated the pregnane X receptor (PXR) and regulated CYP3A and P-glycoprotein.Our aim was to investigate the effect of regular consumption of RRR-a-tocopherol on the activity of CYP3A and P-glycoprotein in vivo.METHODS: In a randomized cross-over study with two phases, 12 healthy volunteers ingested RRR-a-tocopherol 600mg each day or placebo(control) for 14 days. On day 15, a single 7.5mg dose of midazolam and 100mg talinolol was administered with 200 ml water. Plasma concentrations of midazolam,1-OH midazolam and talinolol were determined up to 24h.RESULTS: There was considerable individual variation in AUC and Cmax. The AUC_0-8(P=0.455) and C_max(P=0.950) of midazolam and AUC_0-8(P=0.967) and C_max(P=0.096) of 1-OH midazolam showed no difference between two groups. But Coadministration of RRR-a-tocopherol obviously decreased the area under the curve [AUC(0 24h)] of talinlol (2104.059±669.79ng.h/ml VS 2914.455±1061.11 ng.h/ml, P＜0.05), and significantly decreased Cmax of talinlol (249.38±68.59ng/ml VS 405.73.00±213.60ng/ml, P＜0.05)。with the influence being more prominent in female subjects.CONCLUSIONS: Even 600mg RRR- a-tocopherol, taken daily for 2 weeks, significantly induces the p-glycoprotein substrate talinlol. But we failed to find any influence on the disposition of midazolam. Great attention should be paid when the drug interaction occurs between RRRa-tocopherol and P-glycoprotein substrates, especially for woman.