Comparative Plasma Pharmacokinetics of Ziyuglycoside I from Sanguisorba Officinalis L. between Leukopenia and Normal Rats via UHPLC-MS/MS

Abstract

Objectives: Ziyuglycoside I (ZgI), one of the main active ingredients of Diyushengbai tablet made from Sanguisorba officinalis L., has been proved to relieve leukopenia. In our study, we compared the difference of pharmacokinetics of ZgI between normal and leukopenia rats.Materials and methods: 24 rats were divided into four groups, low and high dose (orally taken ZgI 5 or 20 mg/kg, respectively) control or leukopenia groups, induced by intraperitoneal injection of 70 mg/ kg Cyclophosphamide (CY) twice. plasma samples were collected from orbital venous plexus at 0, 5, 10, 20, 40, 60 min, 1.5, 2, 4, 8, 12, 24, 48 h after oral administrated of ZgI, and concentrations of ZgI were analyzed by Ultra-High Performance Liquid Chromatography-tandem Mass-spectrometry (UHPLC-MS/MS).Results: Compared with20 mg/kg normal group, peak time (T max ) was significantly shortened (0.93 h to 0.33 h) and maximum Concentration (C max ) was remarkably decreased (7.96 ng/L to 3.40 ng/L) in 20 mg/kg leukopenia group, on the contrary, elimination half-life (T 1/2β ) in it was obviously prolonged (5.02 h to 18.51 h). However, there were no clearly differences in distributed half-life (T 1/2α ) and area under the plasma concentration vs. time curve from zero to last sampling time (AUC 0-t ) between20 mg/kg leukopenia and control group (p>0.05). All above changes were similar between 5 mg/kg model and control group, except C max were nearly equal between them. Interestedly, there was also no evidently difference between the two leukopenia groups. Conclusion:The pharmacokinetic process especially absorption and metabolism of ZgI were evidently influenced by leukopenia. Our study may provide guidance for clinical use of Diyushengbai tablet and development of ZgI as an agent for the treatment of leukopenia.