The Effect Of Schisandra Chinensis Baill On P-glycoprotein Transport Ability And CYP3A4 Metabolism Activity In Vivo

AIMS: To investigate the effect of Schisandra chinensis Baill onP-glycoprotein and CYP3A4 in vivo activity.METHODS: We genotyped 165 subjects for the MDR1 variant 3435(C→T). An open, randomized, 2-period crossover study was performed in 12healthy male volunteers. Every volunteers ingested orally, once a day for13 days, Schisandra chinensis Baill 3 pill or placebo (control.) On day14th, a single 100mg talinlor tablet and 7.5mg midazolam tablet wasadministrated orally. Plasma concentration of talinlor and midazolam, 1'-OHmidazolam was determined over 24 h..RESULTS: Coadministration of Schisandra chinensis Baillobviously increased the area under the curve [AUC(0~ 24)] of talinlol(3425.20±1751.69 ng.h/ml VS2253.80±698.62 ng.h/ml, P＜0.05), andnotably increased the area under the curve AUC0～∝(6276.45±6426.25ng.h/ml VS2827.08±872.24 ng.h/ml,P＜0.05, and significantly increasedCmax of talinlol(379.82±180.10 ng/mlVS 292.59±108.22ng/ml, P＜0.05),and obviously increased the area under the curve [AUC(0~24)] ofmidazolam (146.71±57.52 ng.h/ml VS 110.80±41.02 ng.h/ml, P＜0.01),and significantly increased AUC(0～8) of midazolam (152.28±59.62 VS113.25±42.67 ng.h/ml, P＜0.01) and Cmax increased significantly(52.67±18.14 VS 41.00±12.38, P＜0.01) and T1/2 increased significantly(2.85+1.46 VS 2.20±1.07, P＜0.05).CONCLUSIONS:In conclusion, Schisandra chinensis Baillsignificantly inhibit the p-glycoprotein substrate talinlol and CYP3A4substrate midazolam. In different genotype groups in MDR1 3435 variant,AUC0～24h and Cmax had the tend of increasing, but had not significantdifference. It is very important to pay great attention when the druginteraction occur between schisandra chinensis baill and P-glycoproteinsubstrates and CYP3A4 substrate.