Repeated administration of Sailuotong, a fixed combination of Panax ginseng, Ginkgo biloba, and Crocus sativus extracts for vascular dementia, alters CYP450 activities in rats.

摘要: Abstract Background Sailuotong (SLT) is a standard Chinese preparation made from extracts of Panax ginseng (ginseng), Ginkgo biloba (ginkgo), and Crocus sativus (saffron). Preliminary clinical trials animal experiments have demonstrated that SLT could improve cognition vascular dementia (VD). Purpose To avoid incident drug-drug interaction which easily encountered in patients VD, the potential influence on main drug-metabolic cytochromes P450 enzymes (CYP450) was investigated. Method A “cocktail probes” approach employed to evaluate activities CYP450. rapid selective analysis method developed examine 5 CYP probe drugs their specific metabolites plasma by using online SPE followed single LC-MS/MS run. After pretreatment for 2 weeks with SLT, ginseng, gingko, saffron or water (control), cocktail solution containing caffeine, losartan, omeprazole, dextromethorphan midazolam given rats orally. The obtained at different time intervals then measured concentration probes SPE-LC-MS/MS method. Activity five isozymes estimated comparing pharmacokinetics substrates (caffeine/paraxanthine CYP1A2, losartan/E-3174 CYP2C11, omeprazole/5-hydroxyl omeprazole CYP2C6, dextromethorphan/dextrophan CYP2D2 midazolam/1-hydroxyl CYP3A1/2) between control drug treatment groups. Result Compared group, repeated administration induced CYP1A2 enhancing AUC paraxanthine / caffeine to144%. attributed its herbal component large extent. Meanwhile, metabolic ability towards losartan significantly elevated gingko group 31% 25% respectively, indicating weak induction CYP2C11 rats. showed lack 2C6 all treated In terms CYP3A1/2, decreased ratio 1-hydroxyl 39% extended half-life apparently. Besides, systematic exposure suggested inhibition metabolism CYP3A1/2 likely secondary absorption intestinal level. CYP3A cooperatively. Conclusion Further observation herb-drug should be considered during application SLT.