Studies On Pharmacokinetics And Drug-Drug Interactions Of Saikosaponin A

1. Absorption mechanism of saikosaponin a across Caco-2 monolayer modeThe Caco-2 cell monolayer drug transport model was used to study the double transport mechanism of saikosaponin a. To explore the effect of saikosaponin a absorption by time and drug concentration, the drug concentration was determined through the use of LC-MS instrument and the Papp was calculated. In the Caco-2 monolayer model, the transport of saikosaponin a from Apical (AP) to Basolateral (BL) was similar to the transport form BL to AP. The main mechanism of the saikosaponin a intestinal absorption in the Caco-2 monolayer model is passive transference.2. Pharmacokinetic study of saikosaponin a in rat plasma by LC-ESI-MS12 rats were given 5 mg·kg-1,iv and 50 mg·kg-1,ig. Drug plasma concentration was determined by LC-ESI-MS and the pharmacokinetic parameters were evaluated by DAS Software. Calibration curve was linear between 0.025～5μg·mL-1 and LOQ was 25 ng·mL-1, the recoveries of saikosaponin a from plasma were higher than 80%, and RSD of inter-day and intra-day assay were limited in 10%. After intravenous administration of 5 mg·kg-1 saikosaponin a, the pharmacokinetic parameters of Tmax, Cmax, AUC(0-t), T1/2, CL and Vd were 5min,1907μg·L-1,64370μg·h-1·mL-1,100.6min,0.0867L·min-1·kg-1,21.89 L·kg-1espectively. The above-mentioned method was sensitive and specific, and suitable for pharmacokinetic studies on saikosaponin a in rats.3. The effect of Xiaochaihu Granule and Chaihu Oral liquid on the pharmacokinetics of intragastrically administered cyclosporine A in rats16 Sprague-Dawley rats were equally divided into two groups by randomized block design according to weight. Each rat was intragastrically administered CsA (10 mg·kg-1,bid). On the sixth day, after each rat was intragastrically administered CsA (10 mg·kg-1), blood samples (0.6mL) were collected from the tail vein at 0,1,2,4,6,8,12,24 and 32 h. From day 6 to day 10, each group began to undergo different pretreatments. The Xiaochaihu group were intragastrically co-administered CsA (10 mg·kg-1) and Xiaochaihu Granule (2g·kg-1), At the same time, The rats in Chaihu group were intragastrically co-administered CsA (10 mg·kg-1) and Chaihu Oral liquid (2g·kg-1), then blood samples were collected according to the schedule of the sixth day. The whole blood concentration of CsA was determined by HPLC. Main pharmacokinetic parameters were calculated and compared by statistic analysis. Before co-administrated with CsA, no significantly different pharmacokinetic parameters of CsA were found for the two single administration groups. After co-administrated with CsA, AUC0-32h and Cmax were increased significantly (P<0.05 and P<0.01); T1/2βand V/F were not apparently influenced. There was no significant change in other parameters. It was indicated that both of the two preparations could apparently increase the intragastric absorption extent of CsA, while they almost had no effect on the drug elimination process.