Pharmacokinetics and brain distribution differences of baicalin in rat underlying the effect of Panax notoginsenosides after intravenous administration

Baicalin(BA) is the most well-known flavonoid present in Radix Scutellariae. The aim of this study was to explore whether the pharmacokinetic behavior of BA in rat brain can be affected by Panax notoginsenosides(PNS), and to assess the possible mechanism for the observed effects. Specific HPLC and HPLC/MS/MS methods were developed and validated for the determination of BA in the rat plasma and brain using carbamazepine as an internal standard. BA was found to enter rat brain quickly after a single intravenous dose. When co-administered with PNS, clearance(CL) of BA from rat plasma decreased by 50.00%, while the area under the curve AUC0-t and AUC0-∞ increased 94.69% and 87.68%, respectively. On the other hand, some pharmacokinetic parameters of BA in rat brain had obvious differences after PNS was administered, such as an increase in Tmax from 5 min to 15 min, an increase in AUC0-t and AUC0-∞ by 42.75% and 29.39%, respectively, as well as a decrease in CL by 27.95%. Together, these results indicate that PNS can decrease the elimination rate of BA from rat plasma, promote the penetration of BA into rat brain, increase the concentration and slow down the elimination of BA from rat brain. The data provide important information that compatibility with PNS can promote the consequent effects of BA for the treatment of encephalopathy.

Stability of Xuesaitong capsules in gastrointestinal lavage fluid

Objective:To obtain a formulation with high bioavailability through evaluation of the stability of three types of Xuesaitong capsules in the stomachs and intestines of rats.We compared the stability of the Panax notoginsenoside R1 as well as the ginsenosides Rg1,Rb1,Re,and Rd in different formulations.Methods:Artificial stomach fluid(ASF)and artificial intestinal fluid(AIF)were prepared.Stability of three types of Xuesaitong capsules was examined for 4 h in stomachs and 24 h in intestines.Samples were analyzed at different times by high-performance liquid chromatography.Percent content of NGR1,GRg1,GRb1,GRe,and GRd at different times was calculated.Results:Hard capsules incubated in ASF disintegrated within 2e3 min,whereas soft capsules disintegrated within 7e8 min.Components in hard capsules were dissolved rapidly in water,with content of each compound reaching 90%in 5 min,and degradation of each compound reaching 30e50%after incubation for 240 min.Dissolution and degradation of each component in soft capsules with a water-soluble base tended to balance at 30 e90 min.Contents in soft capsules with a lipid-soluble base showed slow dissolution after ASF incubation for 120 min.Five saponins in identical types of capsules incubated in ASF had similar stability curves.Contents of hard capsules and soft capsules with a watersoluble base degraded rapidly within 30 min and reached a plateau when Xuesaitong capsules were incubated in AIF.